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Background: Burnout affects >50% of physicians, especially women. This study aimed to examine how negative workplace interactions can predict burnout, and whether positive social interactions can mitigate risk. Materials and Methods: In a study of 1627 physician mothers who responded to a survey by the Physician Moms Group, an online Facebook group, we first examined the association between workplace sexual harassment and burnout. In an embedded experiment, we then measured the causal impact of priming perceived social support and connectedness on the three dimensions of employee burnout. Results: Two-thirds of respondents reported having experienced sexual harassment in the past year. Sexual harassment by patients was associated with 0.27 points higher emotional exhaustion, one dimension of burnout (95% confidence interval [CI] 0.12–0.41), equivalent to the predicted impact of an additional 22 weekly work hours on emotional exhaustion. Sexual harassment by patients was also associated with 0.40 points higher patient depersonalization, another dimension of burnout (95% CI 0.27–0.53). Sexual harassment by colleagues was associated with 0.16 points higher emotional exhaustion (95% CI 0.02–0.30), but not other dimensions of burnout. We found no significant relationship between experiences of sexual harassment and levels of personal accomplishment (the third dimension of burnout) among this sample. Priming physician mothers to reflect on their connectedness with other physician mothers significantly increased their sense of personal accomplishment. The priming intervention did not yield a significant effect on emotional exhaustion or depersonalization. Conclusions: Negative and positive social interactions each affect different dimensions of burnout. Sexual harassment—a pervasive type of negative social interaction—strongly predicts emotional exhaustion and depersonalization. Reflecting on social connectedness—a type of positive social interaction—can improve one's sense of personal accomplishment with an effect similar in magnitude to more intensive in-person interventions, suggesting that social connectedness through online groups merits further consideration as a tool to mitigate burnout.