This study examined the effects of muscle mass on mortality in patients with acute kidney injury requiring continuous renal replacement therapy. It was conducted in eight medical centers between 2006 and 2021. The data of 2200 patients over the age of 18 years with acute kidney injury who required continuous renal replacement therapy were retrospectively collected. Skeletal muscle areas, categorized into normal and low attenuation muscle areas, were obtained from computed tomography images at the level of the third lumbar vertebra. Cox proportional hazards models were used to investigate the association between mortality within 1, 3, and 30 days and skeletal muscle index. Sixty percent of patients were male, and the 30-day mortality rate was 52%. Increased skeletal muscle areas/body mass index was associated with decreased mortality risk. We also identified a 26% decreased risk of low attenuation muscle area/body mass index on mortality. We established that muscle mass had protective effects on the mortality of patients with acute kidney injury requiring continuous renal replacement therapy. This study showed that muscle mass is a significant determinant of mortality, even if the density is low.