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To assess the prevalence of depressive symptoms and difficulty with pain in retired professional football players, difficulties with the transition from active athletic competition to retirement, perceptions of barriers to receiving assistance for those difficulties, and recommended programs to provide such assistance.Survey sent to 3377 retired members of the National Football League Players Association (NFLPA), with usable responses received from 1617 members (functional response rate, 48.6%).Respondents were categorized as experiencing no to mild depression (N = 1366; 84.5%) or moderate to severe depression (N = 237; 14.7%). Respondents were also categorized according to whether they reported difficulty with pain as not or somewhat common (N = 837; 51.8%) versus quite or very common (N = 769; 47.6%). Respondents most frequently reported trouble sleeping, financial difficulties, marital or relationship problems, and problems with fitness, exercise, and aging, all of which were strongly correlated with the presence of moderate to severe depression and with quite or very common difficulty with pain. The same difficulties were even more commonly experienced by respondents who reported both moderate to severe depression and quite or very common difficulty with pain, compared with those who reported low scores in both domains.Retired professional football players experience levels of depressive symptoms similar to those of the general population, but the impact of these symptoms is compounded by high levels of difficulty with pain. The combination of depression and pain is strongly predictive of significant difficulties with sleep, social relationships, financial difficulties, and problems with exercise and fitness. A hypothesis explaining this association is that significant musculoskeletal disability and chronic pain interferes with physical activity and fitness during retirement and increases the risk of depression.