To inform parent-mediated intervention models, this study assessed if family affectedness (i.e., elevated autism symptoms in more than one child) was associated with maternal self-reported social difficulties (as indexed by the Social Responsiveness Scale; SRS-2), and social interactions during play. As part of a prospective study, 71 mothers completed the SRS-2 and a play session. Interactions were coded for a range of prosocial behaviors, including gaze, positive affect, and vocalizations. Overall, mothers with multiple children exhibiting autism symptoms self-reported significantly more social difficulties on the SRS-2, when compared to mothers raising only typically developing children, or one child with autism. However, even with elevated SRS-2 scores, mothers with higher family affectedness demonstrated comparable social exchanges with their children during play.