Bipolar disorder (BD) is a severe, recurrent, and often chronic psychiatric illness associated with significant functional impairment, morbidity, and mortality. Creatine kinase (CK) is an important enzyme, particularly for cells with high and fluctuating energy requirements, like neurons, which has been proposed as potential marker of brain injury. Forty-eight bipolar patients were recruited for assessment of serum CK levels; 18 were in euthymic state, 17 were in manic and 13 in depressive episodes. A healthy comparison group included 41 healthy volunteers. During mania, CK levels were increased in comparison with healthy subjects. On the other hand, no significant differences in CK levels in euthymic and depressive patients were observed. In conclusion, our results suggest that the clinical differences between depressive, manic and euthymic phases of BD are supported also by contrasting levels of CK. However, more studies are necessary to understand the state-dependent differences observed in serum CK activity during the phases of BD.