In socially-monogamous species, intolerance of interactions between a pairmate and a sexual rival (i.e., mate-guarding) promotes the preservation of long-lasting partnerships. One promising neurobiological candidate for the regulation of mate-guarding behavior in monogamous primates is the oxytocin (OT) system, given its established role in both the development of monogamous bonds and the behavioral processes that facilitate the preservation of those bonds. In this study, male and female marmosets were exposed to a same-sex intruder in their home environment during conditions when their pairmate was present and absent, and across three treatment conditions (OT receptor agonist; saline control; OT receptor antagonist). Saline-treated marmosets spent significantly more time in proximity to the intruder, relative to the empty pairmate enclosure, when their pairmate was absent. However, when marmosets received OT they spent less time in proximity to the intruder, indicating that OT may reduce interest in a same-sex stranger in a territorial context. When their pairmate was present, saline-treated marmosets spent equal time in proximity to both intruder and pairmate; yet when they received OT they spent significantly more time in proximity to the intruder, indicating that OT may increase interest in a same-sex stranger in a mate-guarding context. While OT treatment did not directly influence the expression of aggression, OT system manipulations impacted the expression of selective social interest during an intruder challenge, suggesting that OT may enhance adaptive responses to social challenges. Moreover, these findings add to the converging evidence that the OT system regulates behavioral processes that underlie the preservation of established relationships.