Duloxetine, a dual-reuptake inhibitor of serotonin and norepinephrine, has been approved for the treatment of major depressive episodes and for female stress urinary incontinence. At present, only sparse experiences are available regarding antidepressive treatment in patients with a psychotic lifetime diagnose, whereas this group of patients often suffer from major depressive episodes. Here, we describe the first case of a male patient with postpsychotic depression who developed the severe side effect of urinary retention during antidepressive treatment with duloxetine combined with olanzapine. After remission of his psychotic episode, the patient presented with depressed mood, psychomotor inhibition, sleep disturbance, and suicidal ideas. Without changing the antipsychotic therapy, we implemented duloxetine (60 mg/d) and the patient significantly improved. However, he increasingly suffered from obstructive voiding difficulties and complained about a weak urinary stream and incomplete voiding leading to unacceptable dribbling. The urinary retention disappeared completely within 1 week after discontinuation of duloxetine. We switched to venlafaxine (150 mg/d) and were able to keep the depression in remission. This case report demonstrates for the first time the onset of urinary retention in postpsychotic depression and during combined treatment with duloxetine and olanzapine. We therefore suggest increased attention on voiding function in particular if several pharmacological agents are combined.