Objective: The occurrence of thrombocytopenia with valproate and clozapine combination therapy has not been noted in the literature. This case report highlights thrombocytopenia as a potential outcome of drug-drug interaction between valproate and clozapine, and serves to remind practitioners that regular monitoring of platelet counts is necessary in such combination therapy. Method: We report on a patient on valproate therapy who developed thrombocytopenia when clozapine was added to her treatment regime. Results: Thrombocytopenia resolved 1 week after valproate was tailed off and the patient was placed on clozapine monotherapy. Conclusions: A precise pathophysiologic understanding of valproate and clozapine-induced thrombocytopenia is lacking, and further studies are required.