An emerging literature is specifically focusing on the effects of sleep deprivation on aspects of social functioning and underlying neural changes. Two critical facets of social behavior emerge that are negatively impacted by sleep deprivation-self-regulation, which includes behavioral and emotional regulation, and social monitoring, which includes perceiving and interpreting cues relating to self and others. Sleep deprived individuals performing tasks with social components show altered brain activity in areas of the prefrontal cortex implicated in self-control, inhibition, evaluation, and decision-making, in proximity to mesocorticolimbic pathways to reward and emotional processing areas. These cognitive changes lead to increased reward seeking and behaviors that promote negative health outcomes (such as increased consumption of indulgence foods). These changes also lead to emotional disinhibition and increased responses to negative stimuli, leading to reductions in trust, empathy, and humor. Concomitant attentional instability leads to impaired social information processing, impairing individual and team performance and increasing likelihood of error, incident, and injury. Together, changes to reward seeking, the foundational components of social interaction, and interpretation of social cues, can result in unpleasant or deviant behavior. These behaviors are perceived and negatively responded to by others, leading to a cycle of conflict and withdrawal. Further studies are necessary and timely. Educational and behavioral interventions are required to reduce health-damaging behaviors, and to reduce emotionally-laden negative interpretation of sleep-deprived exchanges. This may assist with health, and with team cohesion (and improved performance and safety) in the workplace and the home.