© The Author(s) 2018. Weight stigma is related to lower levels of motivation to exercise in overweight and obesity. This study explored the nature of the relationship between stigma, motivation to exercise and physical activity while accounting for gender differences. Participants were 439 adults with overweight and obesity (mean body mass index = 32.18 kg/m2, standard deviation = 4.09 kg/m2). Females reported significantly more frequent stigma experiences than males. Mediation models found a conditional direct effect of weight stigma for males, with higher frequency of stigma experiences related to higher levels of walking and vigorous physical activity. A conditional indirect effect was found for females for walking, moderate and vigorous levels of physical activity, with higher weight stigma related to lower autonomous motivation, and lower levels of physical activity. Findings suggest that males and females are affected differently by weight-stigma experiences.