In the wake of the COVID-19 pandemic, many nations around the world instituted strict social distancing measures. Although necessary to deter the spread of the virus, these measures may also have had adverse health repercussions by increasing social isolation. Using a national longitudinal study from Canada, in which respondents were surveyed in March 2020 at the beginning of stay-at-home orders and again two months later in May, we show that, at baseline, loneliness was inversely associated with perceptions of self-rated health, and there was a beneficial indirect association between respondents’ number of social network confidants and perceived health through lower levels of loneliness. Between March and May, social network confidants decreased and loneliness increased; these changes were independent of each other and contributed to declines in self-rated health. Greater loneliness at baseline was also associated with declines in self-rated health. Our observations suggest that social distancing during the COVID-19 pandemic impaired social connectedness, thereby resulting in declines in perceptions of health. We conclude by discussing several policy-related implications of our findings.