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Background: People living with human immunodeficiency virus (PLHIV) are at an increased risk for developing cardiovascular disease (CVD). Physical activity and cardiorespiratory fitness in PLHIV are poorly understood., Objective: The aims of this study were to describe physical activity and cardiorespiratory fitness by sex and age and to examine the association between physical activity and cardiorespiratory fitness in PLHIV, controlling for covariates., Methods: Seven hundred two PLHIV participated in a cross-sectional study and completed validated measures of self-reported physical activity (7-day Physical Activity Recall) and cardiorespiratory fitness (6-minute walk test). Participants were recruited from 7 diverse sites in the United States and Thailand, and data were analyzed using descriptive statistics and multiple regression to examine the relationship between physical activity and cardiorespiratory fitness., Results: On average, participants self-reported engaging in 115 minutes of, mostly light (75%), physical activity. Men reported twice the amount of physical activity as women (155 vs 73 minutes, P = .01). Participants' ability to achieve their predicted 6-minute walk test distances was similar between men (68%) and women (69%) (P > .01). For women, vigorous physical activity was associated with a 6.6% increase in cardiorespiratory fitness and being temporarily unemployed was associated with an 18% decline in cardiorespiratory fitness. Cardiorespiratory fitness increased with age (P < .01)., Conclusions: Weekly physical activity of people living with human immunodeficiency virus averaged 85 minutes of mostly light activity, well below the recommended 150 minutes of moderate activity. Vigorous physical activity was associated with improved cardiorespiratory fitness in women, but not men. Although PLHIV would benefit from interventions to increase physical activity, our data suggest a need to develop sex-specific physical activity strategies.