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Social isolation and disconnectedness increase the risk of worse mental health, which might suggest that preventive health measures (i.e., self-quarantining, social distancing) negatively affect mental health. This longitudinal study examined relations of self-quarantining and social distancing with mental health during the COVID-19 pandemic. A U.S. national sample (N = 1,011) completed eight weekly online surveys from March 20, 2020 to May 17, 2020. Surveys assessed self-quarantining, social distancing, anxiety, and depression. Fixed-effect autoregressive cross-lagged models provided a good fit to the data, allowing for disaggregation of between-person and within-person effects. Significant between-person effects suggested those who engaged in more self-quarantining and social distancing had higher anxiety and depression compared to those who engaged in less social distancing and quarantining. Significant within-person effects indicated those who engaged in greater social distancing for a given week experienced higher anxiety and depression that week. However, there was no support for self-quarantining or social distancing as prospective predictors of mental health, or vice versa. Findings suggest a relationship between mental health and both self-quarantining and social distancing, but further longitudinal research is required to understand the prospective nature of this relationship and identify third variables that may explain these associations. [ABSTRACT FROM AUTHOR]