This research aimed to associate for the first time in the literature Regulatory Focus and Self-Determination theories to understand the dynamics of physical activity practice in the health context. Two cross-sectional studies were conducted with 603 (Study 1) and 395 (Study 2) French volunteer participants aged from 18 to 69 and 19 to 71 respectively, who were healthy or concerned by a health condition. The main results of structural equation modeling analyses demonstrated that across the two studies, health promotion focus was positively associated with intrinsic motivation (.44 < β < .74, p < .001), integrated regulation (.47 < β < .72, p < .001), identified regulation (.40 < β < .69, p < .001) and introjected regulation (.41 < β < .53, p < .001), whereas health prevention focus was positively related with external regulation (.31 < β < .45, p < .001) and amotivation (.32 < β < .38, p < .001). Boot-strapping analyses main results in Study 2 showed that health promotion focus was indirectly associated with physical activity through intrinsic motivation (95% CI [.02 to .11]), integrated regulation (95% CI [.00 to .08]), identified regulation (95% CI [.00 to .09]) and introjected regulation (95% CI [.04 to .12]), whereas health prevention focus was indirectly associated with physical activity through external regulation (95% CI [.00 to .12]). These studies reveal meaningful associations between Regulatory Focus and Self-Determination theories' variables which support the relevance of associating these two models to understand the processes underlying the physical activity practice.