Mitochondrial dysfunction (MD) is a complex pathophysiological phenomenon, linked with many inherited and acquired diseases. A clinical evaluation of MD requires rather extensive approach, while no gold-standard circulating biomarker has been established so far. Partly produced in mitochondria, creatine thus might be considered as a sensible compound of mitochondrial bioenergetics. Increased plasma creatine perhaps is linked with MD, illustrating disturbances in its utilization in the stressed organelle.