Mitochondrial disorders are caused by impairment of the respiratory chain. Psychiatric features often represent part of their clinical spectrum. However, the real incidence of psychiatric disorders in these diseases is unknown. The aim of this study was to evaluate psychiatric involvement in a group of patients with mitochondrial disorders and without already diagnosed mental illness. Twenty-four patients with mitochondrial disorder and without already diagnosed mental diseases have been studied by means of the mini-international neuropsychiatric interview (MINI) and the newcastle mitochondrial diseases adult scale (NMDAS). In patients with mitochondrial disease, psychiatric conditions were far more common than in general Italian population (about 60 vs. 20-25%), and included major depression, agoraphobia and/or panic disorder, generalized anxiety disorder, social anxiety disorder, psychotic syndromes. Psychiatric involvement did not seem to depend on disease progression. Large, multicenter studies are strongly needed to better characterize the natural history of mitochondrial disorders and of their psychiatric involvement. Moreover, the possibility of mitochondrial diseases should be considered in patients with psychiatric diseases. Finally, we encourage psychiatric evaluation as a routinary approach to mitochondrial patients.