In veterinary medicine, serum creatine-kinase (CK) activity is mostly used to assess skeletal muscle damage. This retrospective study aimed to evaluate the prevalence of increased CK activity in a large, ill-cat population and to characterise associated diseases, clinical and laboratory findings and its prognostic value. Cats with a complete serum biochemistry analysis were consecutively enrolled, divided into two CK activity-based groups (within and above reference interval) and compared. The study included 601 cats. Median serum CK was 402. U/l (range 16-506870). Increased CK (>250. U/l) was observed in 364 (60%) cats, and > 30-fold its upper reference limit in 43 (7%). Cats with increased CK had greater (P≤ 0.05) body weight, and were more likely to have a history of collapse, dyspnoea, abnormal lung sounds, cyanosis, shock and paraplegia, higher median serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities and total bilirubin and triglyceride concentrations, but lower, median total protein, albumin, globulin and cholesterol concentrations and proportion of anorexia than cats with normal CK. Cardiac diseases, trauma, bite wounds, systemic bacterial infections, prior anaesthesia and intramuscular injections were more common (P≤ 0.05) in cats with increased compared to normal CK activity. The hospitalisation period was longer (P= 0.007) and treatment cost and mortality were higher (P< 0.005) in cats with increased CK activity. However, CK activity was an inaccurate outcome predictor (area under the receiver operator characteristics curve 0.58). Increased CK activity is very common in ill cats.