Clozapine is known as the gold standard concerning treatment-resistant psychotic disorders. Due to its high affinity to muscarinergic, adrenergic, and histaminergic receptors, clinicians often see side effects like agranulocytosis, weight gain, or sedation, whereas others like gastrointestinal adverse effects are rare. This case reports describes the case of newly diagnosed colitis following the prescription of clozapine. The diagnosis of clozapine-induced colitis was due to the significantly increased calprotectin value in the stool with >6000 units. Therapy consisted of the discontinuation of clozapine as a triggering agent, while treatment for the general infection was initiated.