We examined the emotional and psychophysiological underpinnings of social interaction in the context of autism spectrum disorder, more specifically, involving participants diagnosed with Asperger syndrome (AS). We recorded participants’ autonomic nervous system (ANS) activation (electrodermal activity, heart rate, and heart rate variability) and facial muscle activation during conversations in two different types of male dyads: (1) ten dyads where one participant has been diagnosed with AS (AS/NT dyads) and (2) nine dyads where both participants are neurotypical (NT/NT dyads). Afterwards, three independent raters assessed continuously each participant’s affiliative and dominant behaviors during the first and last 10 minutes of the conversations. The relationship between the assessed data and ANS responses was examined. We found that, in the NT/NT dyads, a high level of affiliation displayed by the conversational partner calms down the participant when they are actively dominating the interaction. In contrast, when the participants themselves expressed affiliation, their psychophysiological responses indicated increase in arousal, which suggests that the giving of affiliation is physiologically “hard work.” The affiliation-related ANS responses were similar in those NT participants whose conversational partner had AS, while some differences in facial muscle activation did occur in comparison to NT/NT dyads. In the AS participants, in contrast, a high level of affiliation provided by the conversational partner was associated with increase in arousal, suggesting heightened alertness and stress. As for their own affiliative behavior, the AS participants exhibited similar indicators of alertness and stress as the NT participants, but only when their own level of dominance was low. Our results increase understanding of how individuals with AS experience social interaction at the physiological level, and how this experience differs from that in NT individuals. Moreover, our results confirm and further specify our earlier results, where we proposed that affiliation involves the type of “sharing of the burden” that also reverberates in the participants’ bodies.