We report on our experience of treating depression secondary to hypoxic brain injury with the antidepressant vortioxetine to share in the growing body of evidence. Our patient was referred to a community mental health team with depression, amotivation and memory difficulties following a myocardial infarction and cardiac arrest 2 years prior. Regardless of motor recovery, major cognitive deficits remained; however, neurorehabilitation was impossible due to severe depression. We tried vortioxetine in the light of two failed antidepressants and saw a remarkable improvement in mood, motivation and engagement.