The authors examined whether the nature of the opponent (computer, friend, or stranger) influences spatial presence, emotional responses, and threat and challenge appraisals when playing video games. In a within-subjects design, participants played two different video games against a computer, a friend, and a stranger. In addition to self-report ratings, cardiac interbeat intervals (IBIs) and facial electromyography (EMG) were measured to index physiological arousal and emotional valence. When compared to playing against a computer, playing against another human elicited higher spatial presence, engagement, anticipated threat, post-game challenge appraisals, and physiological arousal, as well as more positively valenced emotional responses. In addition, playing against a friend elicited greater spatial presence, engagement, and self-reported and physiological arousal, as well as more positively valenced facial EMG responses, compared to playing against a stranger. The nature of the opponent influences spatial presence when playing video games, possibly through the mediating influence on arousal and attentional processes.