Low muscle mass and chronic lung disease are common among people with HIV (PWH), but whether low muscle mass is associated with a faster decline in lung function in this population remains unknown. We aimed to determine the prevalence and associated factors of low muscle mass, and the association between low muscle mass and lung function decline in PWH. Prospective study on PWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study. Skeletal muscle index (SMI) was assessed with computed tomography and low muscle mass was defined as SMI below the lowest 5% of a healthy population. Lung function was measured as forced expiratory volume in 1 second (FEV1) at baseline and two-year follow-up. We used logistic regression to investigate potential risk factors for low muscle mass. Using linear mixed models, we investigated if low muscle mass was associated with a faster FEV1 decline. We included 509 PWH, and 16% had low muscle mass. Older age, male sex, lower body mass index, and high concentrations of interleukin 6 and tumor necrosis factor alpha were associated with low muscle mass. Low muscle mass was not associated with a faster FEV1 decline (35.9 mL/year versus 34.0 mL/year in PWH with and without low muscle mass, respectively; P = 0.69). Almost one in six PWH had low muscle mass, mirroring the general population. Traditional risk factors and inflammatory markers were associated with low muscle mass. We found no association between low muscle mass and a faster FEV1 decline among PWH.