We assess the causal impact of a spontaneous relaxation of social distancing practices on the spread of SARS-CoV-2 in the U.S., while controlling for social mobility and state-imposed social distancing restrictions. Using the quasi-experimental setting created by the U.S. nationwide protests precipitated by George Floyd’s tragic death on May 25, 2020, we document a country-wide increase of over 3·06 cases per day, per 100,000 population, following the onset of the protests (95% CI:2·47–3·65), and a further in-crease of 1·73 cases per day, per 100,000 population, in the counties in which the protests took place (95% CI:0·59–2·87). Relative to the week preceding the onset of the protests, this represents a 61·2% country-wide increase in COVID-19 cases, and a further 34·6% increase in the protest counties. Hence, we conclude that social distancing practices causally impact the spread of SARS-CoV-2. The observed effect cannot be explained by changes in social distancing restrictions and social mobility, and our placebo tests rule out the possibility that this finding is attributable to chance. Our research informs policy makers and provides insights regarding the usefulness of social distancing as an intervention to minimize the spread of SARS-CoV-2.