AbstractAccumulation of fat in the liver and skeletal muscle is associated with obesity and poor health outcomes. Liver steatosis is a characteristic of non-alcoholic fatty liver disease (NAFLD) and myosteatosis, of poor muscle quality in sarcopenia. In this study of 403 men (33–96 years), we investigated associations between the fatty liver index (FLI) and muscle density, as markers of fat accumulation in these organs. We also investigated associations between the FLI and parameters of sarcopenia, including DXA-derived appendicular lean mass (ALM) and handgrip strength by dynamometry. Muscle density was measured using pQCT at the radius and tibia. FLI was calculated from BMI, waist circumference, and levels of triglycerides and gamma-glutamyltransferase. There was a pattern of decreasing muscle density across increasing quartiles of FLI. After adjusting for age and lifestyle, mean radial muscle density in Q4 was 2.1% lower than Q1 (p < 0.001) and mean tibial muscle density was 1.8% lower in Q3 and 3.0% lower in Q4, compared to Q1 (p = 0.022 and < 0.001, respectively). After adjusting for age and sedentary lifestyle, participants in the highest FLI quartile were sixfold more likely to have sarcopenia. In conclusion, our results suggest that fat accumulation in the liver co-exists with fat infiltration into skeletal muscle.