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Previous analyses have primarily focused on patients with relatively mild to moderate deficits. However, outcomes vary among survivors of severe strokes, and the mechanisms of recovery remain poorly understood. This study assesses the association between lesion\u2010induced network disconnection and outcome after severe stroke. Thirty\u2010eight ischaemic stroke patients underwent MRI brain imaging early after stroke and longitudinal clinical follow\u2010up. Lesion information was integrated with normative connectome data to infer individual disconnectome profiles on a localized regional and region\u2010to\u2010region pathway level. Ordinal logistic regressions were computed to link disconnectome information to the modified Rankin Scale after 3\u20136\u2009months. Disconnections of ipsilesional frontal, parietal, and temporal cortical brain areas were significantly associated with a worse motor outcome after a severe stroke, adjusted for the initial deficit, lesion volume, and age. 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