Background: Sarcopenia is thought to be related to an increased risk of non-alcoholic steatohepatitis and advanced liver fibrosis. Our cross-sectional single-center study was designed to analyze the prevalence of sarcopenia in patients with NAFLD and possible influencing factors. Methods: A survey on the presence of sarcopenia, fatigue, anxiety, and depression, along with a quality-of-life (QoL) assessment, was forwarded by email to 189 outpatients. Demographics, anthropometric and clinical data (laboratory test results and abdomen complete ultrasound protocol), performed within 2–4 weeks prior to the enrollment, were obtained. Results: Sarcopenia (defined as SARC-F score ≥ 4) was identified in 17 (15.7%) patients, all of them (100%) females, with median age (interquartile range) 56 (51–64) years. These patients had a poorer metabolic state (greater values of waist and hip circumferences, body mass index, and HOMA-IR) and significantly poorer QoL, specifically, regarding the physical component of health, compared with NAFLD patients without sarcopenia. Multivariate analysis showed that depression (OR = 1.25, 95% CI: 1.02–1.53,p= 0.035) and clinically meaningful fatigue (OR = 1.14, 95% CI: 1.04–1.26,p= 0.008) were the factors independently associated with sarcopenia in patients with NAFLD. Conclusion: Sarcopenia is associated with depression and fatigue rather than with the severity of liver disease alone and may negatively affect QoL in patients with NAFLD.