Obsessive-compulsive disorder (OCD) is a prevalent and clinically significant comorbid condition in patients with bipolar disorder. Treatment of bipolar disorder/OCD patients is challenging. We report the results of an open-label, short-term, prospective investigation of quetiapine monotherapy in 16 patients (three men and 13 women, aged 18-56 years) hospitalized for acute bipolar depression who in addition met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for OCD. The participants were treated with quetiapine in a dose range of 150-600 mg (mean 347 mg) for a mean duration of 4.3 ± 1.4 weeks (range 3-7 weeks). Eleven (68.8%) of the 16 study participants fulfilled the predefined criteria for response, namely a score of 'very much improved' (four patients) and 'much improved' (seven patients) on the Clinical Global Impression - Improvement scale. Treatment with quetiapine was associated with a statistically significant decrease from baseline in the relevant rating scales for the assessment of depressive, manic and OCD symptoms. Quetiapine was well tolerated. The most frequently reported side effects were sedation, orthostatic hypotension and constipation. Durability of the positive therapeutic effect of quetiapine monotherapy in patients with bipolar disorder/OCD comorbidity and the necessity for subsequent augmentation with anti-OCD agents need to be addressed in future controlled studies.