We sought to compare the musculoskeletal symptoms and immune markers found in chronic hepatitis C (HCV) and nonalcoholic fatty liver disease (NAFLD). Patients with HCV or NAFLD answered a questionnaire and donated serum for autoantibody testing. Univariate analysis between the HCV and NAFLD groups revealed joint pain in 67% of the HCV group and 65% of the NAFLD group. Those with joint pain reported inflammatory characteristics that were similar between the groups. The presence of a positive rheumatoid factor and cryoglobulins was higher in the HCV group, however both groups had a similar prevalence of a low positive antinuclear antibody (ANA). We conclude that the NAFLD group reported a higher amount of joint pain and inflammatory joint symptoms than anticipated. We were unable to determine a variable that predicted the presence of joint pain. Therefore, more investigation is needed to determine whether these findings are due to liver disease alone.