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Ninety individuals filled depression (Patient Health Questionnaire 9, PHQ\u20109) and PTSD\u2010associated anxiety (PTSD Checklist\u2010Military Version, PCL\u2010M) questionnaires. In 40 patients, a multiplex assay system was used to quantify 23 inflammatory proteins in tears. In a separate group of 50 individuals, liquid chromatography\u2010mass spectrometry was performed on meibum and tears to quantify 34 species of sphingolipids, encompassing ceramides, monohexosyl ceramides and sphingomyelins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mean age of the population was 59.4\u2009\u00b1\u200911.0\u2009years; 89.0% self\u2010identified as male, 34.4% as White, 64.4% as Black, and 16.7% as Hispanic. The mean PHQ\u20109 score was 11.1\u2009\u00b1\u20097.6, and the mean PCL\u2010M score was 44.3\u2009\u00b1\u200919.1. Symptoms of depression and PTSD\u2010associated anxiety were highly correlated (<jats:italic>\u03c1<\/jats:italic> =0.75, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Both PHQ9 and PCL\u2010M scores negatively correlated with multiple sphingolipid species in meibum and tears. In multivariable models, meibum Monohexosyl Ceramide 26:0 (pmol), tear Ceramide 16:0 (mol%), meibum Monohexosyl Ceramide 16:0 (mol%), and tear Ceramide 26:1 (mol%) remained associated with depression and meibum Monohexosyl Ceramide 16:0 (mol%), meibum Monohexosyl Ceramide 26:0 (pmol), tear Sphingomyelin 20:0 (mol%), and tear Sphingosine\u20101\u2010Phosphate (mol%) remained associated with PTSD\u2010associated anxiety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Certain meibum and tear sphingolipid species were related to mental health indices. 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