Objectives
The emergence of the coronavirus disease 2019 (COVID-19) pandemic and subsequent lockdowns and social distancing measures adopted worldwide raised questions about the possible health effects of human social isolation.

Methods
We conducted a systematic review on PubMed, Scopus, and Embase electronic databases using terms related to human social isolation – defined as the isolation of an individual from regular routines and usual social contact – and psychological stress, searching for simulated or naturalistic isolation environments. We present the main results, as well as the validity and limitations of each model. PROSPERO registry number: CRD42021241880.

Results
Despite the diversity of contexts reviewed, some outcomes almost ubiquitously relate to psychological stress, i.e., longer periods, expectation of a longer period, confinement, lack of social interaction, and support. Based on the results, and considering that most studies were not designed for the purpose of understanding isolation itself, we propose a group of recommendations for future experimental or naturalistic research on the topic.

Conclusion
Evidence on the impact of different situations in which individuals are subjected to social isolation can assist in development of directed preventive strategies to support people under similar circumstances. Such strategies might increase the general public’s compliance with social distancing as a non-pharmacological intervention for emerging infectious diseases.