To determine cross-sectional and prospective associations between loneliness and physical activity, and to evaluate the roles of social control and emotion regulation as mediators of these associations.A population-based sample of 229 White, Black, and Hispanic men and women, age 50 to 68 years at study onset, were tested annually for each of 3 years.Physical activity probability, and changes in physical activity probability over a 3-year period.Replicating and extending prior cross-sectional research, loneliness was associated with a significantly reduced odds of physical activity (OR = 0.65 per SD of loneliness) net of sociodemographic variables (age, gender, ethnicity, education, income), psychosocial variables (depressive symptoms, perceived stress, hostility, social support), and self-rated health. This association was mediated by hedonic emotion regulation, but not by social control as indexed by measures of social network size, marital status, contact with close ties, group membership, or religious group affiliation. Longitudinal analyses revealed that loneliness predicted diminished odds of physical activity in the next two years (OR = 0.61), and greater likelihood of transitioning from physical activity to inactivity (OR = 1.58).Loneliness among middle and older age adults is an independent risk factor for physical inactivity and increases the likelihood that physical activity will be discontinued over time.