We present the challenging differential diagnosis of an extreme leukocytosis noted at hospital admission of a patient with severe lactic acidosis and acute kidney injury secondary to metformin overdose. Laboratory and imaging work-up ruled out an infectious or malignant cause for severely increased leukocytes count; thus, it was established that the process of leukocyte demargination was the main cause of increased count of leukocytes. Discussion of available literature data is also presented. Our case report highlights the importance for clinicians to be aware of this possible spurious increase of leukocytes in acute non-infectious stressful conditions in order to avoid unnecessary antibiotics.