Sulbutiamine is a precursor of thiamine that crosses the blood-brain barrier. The modulatory effects on both dopaminergic and glutamatergic transmissions within the prefrontal cortex could play a pivotal role in the therapeutic action of sulbutiamine. Sulbutiamine is currently used for the treatment of fatigue, exhaustion and asthenia in physical and psychiatric disorders; however, it does not have any psycho-stimulant properties. While sulbutiamine has no anti-depressive effect, it exhibits several psychotropic effects such as a decrease in psycho-behavioural inhibition occurring in major depressive disorder. In this report, we describe a possible case of sulbutiamine-triggered manic attack in a patient with major depressive disorder, who later developed bipolar I disorder with spontaneous manic episodes. To our knowledge, this is the first possible case of sulbutiamine-triggered manic attack at the proper therapeutic dosage of sulbutiamine in a major depressive patient.