Background: The COVID-19 pandemic forced social distancing to decelerate the virus spread. This study evaluated the impact of social distancing imposed by COVID-19 on Brazilians’ mental health and quality of life (QoL). Methods: In this cross-sectional community-based online survey, data from 1,156 volunteers were gathered between May 11 and June 3, 2020. We considered independent variables the sociodemographic and clinical characteristics, the LOT-R for Optimism/Pessimism constructs, and the Brief Scale for Spiritual/Religious Coping. Dependent variables were the PHQ-9 for depressive symptoms; the GAD-7 for anxiety disorder; and the WHOQOL-BREF. The presence of depressive and anxiety disorder was estimated with logistic regression. Multivariate GLM assessed the effects of independent variables on the WHOQOL-BREF domains. Outcomes: There was a high prevalence of depressive symptoms (41.9%) and anxiety disorder (29.0%). Negative spiritual/religious coping was positively correlated with depressive symptoms (OR, 2.14; 95%CI, 1.63-2.80; p