Hyponatremia may be a risk factor for rhabdomyolysis, but the association is not well defined and may be confounded by other variables. The aims of this study were to determine the prevalence and strength of the association between hyponatremia and rhabdomyolysis and to profile patients with hyponatremia. In a cross-sectional study of 870 adults admitted to hospital with rhabdomyolysis and a median peak creatine kinase of 4064 U/L (interquartile range, 1921–12,002 U/L), glucose-corrected serum sodium levels at presentation showed a U-shape relationship to log peak creatine kinase. The prevalence of mild (130–134 mmol/L), moderate (125–129 mmol/L), and severe (<125 mmol/L) hyponatremia was 9.4%, 2.5%, and 2.1%, respectively. We excluded patients with hypernatremia and used multivariable linear regression for analysis (n = 809). Using normal Na+ (135–145 mmol/L) as the reference category, we estimated that a drop in Na+ moving from one Na+ category to the next was associated with a 25% higher creatine kinase after adjusting for age, alcohol, illicit drugs, diabetes, and psychotic disorders. Multifactorial causes of rhabdomyolysis were more common than single causes. The prevalence of psychotic and alcohol use disorders was higher in the study population compared to the general population, corresponding with greater exposure to psychotropic medications and illicit drugs associated with hyponatremia and rhabdomyolysis. In conclusion, we found an association between hyponatremia and the severity of rhabdomyolysis, even after allowing for confounders.