Post‑stroke depression (PSD) is the most common neuropsychiatric complication of stroke, such that it can occur in one‑third of stroke survivors. It has been tried to be explained by the disruption in the neural circuits involved in the mood regulation in the setting of some additional clinical risk factors. However, there is no consensus in this regard. Herein, we present a 58‑year‑old male patient presenting with isolated psychotic depression which was finally found to be associated with acute ischemic stroke of bilateral centrum semiovale. This report constitutes an extremely rare illustration of acute onset organic psychotic depression which was clearly demonstrated to be associated with ischemic stroke. Through the presentation of this patient and limited literature, we propose some discussions regarding the pathophysiology of PSD. We also remark the need for future reports of neuroimaging methods to clarify the unknown neural correlates in these manifestations.