This is a cross-sectional study investigating the factors affecting brazilians’ self-rated health during the COVID-19 pandemic, based on data from the web-based behavior survey. Carried out from April 24 to May 24, 2020, the survey recruited participants by a chain sampling procedure. Its outcome was the worsening of self-rated health during the pandemic. Statistical analysis was based on a hierarchical model of determination. Logistic regression models were used to test the associations between sociodemographic characteristics, pre-existing health conditions, lifestyle indicators and intensity of social restraint measures, and biological and psychological issues during the pandemic. From the total sample of 45,161 participants, 29.4% reported worsening of health state during this period. After adjusting for hierarchical distal factors, the health problems mostly associated with worsening health state were: bad self-rated health (adjusted OR = 4.35, p < 0.001), health care seeking for mental health problem (adjusted OR = 3.95, p < 0.001), and for COVID-19 (adjusted OR = 3.60, p < 0.001). People who experienced sleep problems, worsening of back pain, depression and at least one flu symptom during the pandemic were twice as likely to report worsening of health status. Sedentary and eating behaviors and adherence to social distancing measures showed significant correlation with the outcome. There exists a relation between social, biological, and psychological factors, mediated by lifestyles and variables pertaining to confinement. Altogether, these factors have negatively affected self-rated health during the COVID-19 pandemic in Brazil.