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Prospective cohort study of preterm newborns (PTNB) without perinatal hypoxia, Apgar\u2009&gt;\u20096 at 5\u00a0min, and oxygen needs on the third day of life. We compared melatonin levels at day 3 of life in different groups of non-hypoxic preterm infants (Student\u2019s <jats:italic>t<\/jats:italic>-tests, Mann-Whitney <jats:italic>U<\/jats:italic>, and chi<jats:sup>2<\/jats:sup>) and analyzed the relationship of melatonin with GA, birth weight, neonatal pain (Premature Infant Pain Profile (PIPP) scale), caffeine treatment, parenteral nutrition, or the development of free radical diseases (correlation study, linear regression) and factors associated with moderate\/intense pain and free radical diseases (logistic regression analysis). Sixty-one preterm infants with gestational age (GA) of 30.7\u2009\u00b1\u20092.0 weeks with no oxygen requirements at day 3 of life were studied with plasma melatonin levels of 33.8\u2009\u00b1\u200912.01 pg\/ml. Preterm infants weighing\u2009&lt;\u20091250\u00a0g at birth had lower plasma melatonin levels (<jats:italic>p<\/jats:italic>\u2009=\u20090.05). Preterm infants with moderate or severe pain (PPIPP\u2009&gt;\u20095) have lower melatonin levels (<jats:italic>p<\/jats:italic>\u2009=\u20090.01), and being preterm with PIPP\u2009&gt;\u20095 is associated with lower plasma melatonin levels (<jats:italic>p<\/jats:italic>\u2009=\u20090.03). Being very preterm (GA\u2009&lt;\u200932 GS), having low weight for gestational age (LWGA), receiving caffeine treatment, or requiring parenteral nutrition did not modify melatonin levels in non-hypoxic preterm infants (<jats:italic>p<\/jats:italic>\u2009=\u2009NS). Melatonin on day 3 of life in non-hypoxic preterm infants is not associated with later development of free radical diseases (BPD, sepsis, ROP, HIV, NEC).\n<\/jats:p><jats:p><jats:italic>       Conclusion<\/jats:italic>: We observed that preterm infants with moderate to severe pain have lower melatonin levels. These findings are relevant because they reinforce the findings of other authors that melatonin supplementation decreases pain and oxidative stress in painful procedures in premature infants. Further studies are needed to evaluate whether melatonin could be used as an analgesic in painful procedures in preterm infants.\n<\/jats:p><jats:p><jats:italic>      Trial registration<\/jats:italic>: Trial registration was not required since this was an observational study.\n<jats:table-wrap><jats:table><jats:tbody>\n                    <jats:tr>\n                      <jats:td colspan=\"2\"><jats:bold>What Is Known:<\/jats:bold><jats:italic>\u2022 Melatonin is a potent antioxidant and free radical scavenger in newborns under stress conditions: hypoxia, acidosis, hypotension, painful procedures, or parenteral nutrition.<\/jats:italic><jats:italic>\u2022 Pain stimulates the production of melatonin.<\/jats:italic><jats:italic>\u2022 Various studies conclude that melatonin administration decreases pain during the neonatal period.<\/jats:italic><jats:bold>What Is New:<\/jats:bold><jats:italic>\u2022 Non-hypoxic preterm infants with moderate to severe pain (PIPP&gt;5) have lower levels of melatonin.<\/jats:italic><jats:italic>\u2022 Administration of caffeine and treatment with parenteral nutrition do not modify melatonin levels in non-hypoxic preterm infants.<\/jats:italic><\/jats:td>\n                    <\/jats:tr>\n                  <\/jats:tbody><\/jats:table><\/jats:table-wrap><\/jats:p>","DOI":"10.1007\/s00431-024-05632-1","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T11:03:12Z","timestamp":1717671792000},"page":"3607-3615","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lower plasma melatonin levels in non-hypoxic premature newborns associated with neonatal pain"],"prefix":"10.1007","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8133-6328","authenticated-orcid":false,"given":"Cristina","family":"S\u00e1nchez-Borja","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4749-0521","authenticated-orcid":false,"given":"Delia","family":"Crist\u00f3bal-Ca\u00f1adas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Isabel","family":"Rodr\u00edguez-Lucenilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8370-338X","authenticated-orcid":false,"given":"Antonio","family":"Mu\u00f1oz-Hoyos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0164-9648","authenticated-orcid":false,"given":"Ahmad","family":"Agil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda \u00c1ngeles","family":"V\u00e1zquez-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0219-4745","authenticated-orcid":false,"given":"Tesif\u00f3n","family":"Parr\u00f3n-Carre\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5917-7404","authenticated-orcid":false,"given":"Bruno Jos\u00e9","family":"Nievas-Soriano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9924-407X","authenticated-orcid":false,"given":"Antonio","family":"Bonillo-Perales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6843-0245","authenticated-orcid":false,"given":"Juan Carlos","family":"Bonillo-Perales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,6]]},"reference":[{"key":"5632_CR1","doi-asserted-by":"publisher","first-page":"12504","DOI":"10.3390\/ijms222212504","volume":"22","author":"L Cannav\u00f2","year":"2021","unstructured":"Cannav\u00f2 L, Perrone S, Viola V et al (2021) Oxidative stress and respiratory diseases in preterm newborns. 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