PURPOSE: To investigate the prognostic significance of low serum creatine kinase (CK) activity in intensive care unit patients. MATERIALS AND METHODS: The study population consisted of 1899 patients, divided in a "normal" (CK > 20 U/L) and "low" CK group (CK ≤ 20 U/L). The latter group was divided into 2 subgroups by duration of CK activity decrease. Measurement of routine clinical chemistry parameters, calculation of critical care severity scores, and registration of length of stay and mortality rates were performed. RESULTS: The proportion of patients showing a low serum CK activity for at least 1 day was 15.5%. In this group, 24.5% had a prolonged CK activity decrease for at least 5 days. Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were lower in the normal than in the low CK group (P < .0001) and higher in the prolonged CK activity decrease group in comparison with the short-term CK activity decrease group (P < .0001, P = .001). A low serum CK activity was an independent predictor of mortality. Kaplan-Meier analysis showed an overall survival in the low CK group of 243 ± 152 vs 291 ± 139 days in the normal CK group (P < .0001). CONCLUSIONS: Low serum CK activities are associated with a higher severity of illness and higher mortality rates.