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Social isolation (SI) stress results from a combination of intrinsic and environmental factors and is associated with a variety of negative developmental outcomes. Oxytocin (OXT) might play a role in the consequences of SI in the brain and periphery. We conducted a systematic review and meta-analysis to compile data about the effects of SI in the oxytocinergic system of rats and mice, and its relation to behavioral alterations. Five databases (EMBASE, PsychNet, PubMed, Scopus, and Web of Science) were searched in March 2021, using ("Social Isolation" AND (mouse OR rat) AND (oxytocin OR oxytocin receptor)). This review followed the PRISMA guidelines, including registration in PROSPERO, and risk of bias assessment. The twelve articles included in this review indicated that SI was associated with decreased OXTR levels, resulting in behavioral alterations like increased aggression and anxiety-like behavior, hyperactivity, and diminished social behaviors and memory. No significant effects on OXT levels were observed. Administration of synthetic OXT or its agonists partially decreases those unwanted behaviors to similar levels of control animals., (Copyright © 2022 Elsevier Ltd. All rights reserved.)