Resilience is an individual characteristic that protects mental health. However, its impact on the lives of Brazilian physiotherapists during COVID-19 is not known. This study aimed to analyze whether resilience modulates the perceived quality of life (QoL) and subjective happiness (SH) of physiotherapists who work with COVID-19 patients, compared with those who do not. A cross-sectional study was conducted between 22 August and 22 October 2020. Physiotherapists working in critical and non-critical hospital sectors were invited to participate in the study. The participants completed sociodemographic questionnaires and were graded on the 14-item Resilience Scale, 36-item Short-Form Health Survey (SF-36), and the Subjective Happiness Scale. In total, 519 physiotherapists were enrolled in the study. Physiotherapists with low resilience who worked with COVID-19 patients reported lower scores on the SF-36 subscales (except for social functioning) and the Subjective Happiness Scale, compared with those with high resilience who did not work with COVID-19 patients. These responses were modulated by age, sex, absence from work, receipt of personal protective equipment, host leadership, and practice and maintenance of regular physical activity. In conclusion, physiotherapists with low resilience who worked with COVID-19 patients presented lower perceptions of QoL and SH, compared with the other study participants.