Objectives: The study assessed quality of life and depression in working people during COVID-19 pandemic, relative to their physical activity. Material and Methods: The study involved 1194 people living in south-eastern Poland, and assessed life satisfaction (Life Satisfaction Questionnaire – 9 [LISAT-9]), quality of life (World Health Organization Quality of Life – BREF [WHOQoL-BREF]), depression (Beck Depression Inventory [BDI]) and physical activity. Results: The respondents on average scored 4.32 in LISAT-9; respectively 66.2, 68.3, 69.6 and 63.5 in physical, psychological, social and environment domains of WHOQoL-BREF and 9.2 in BDI. Regularly performed physical activity positively affected the scores in all the psychometric tests in women with higher and secondary education and in men with vocational education. Women presented lower life satisfaction, poorer quality of life and higher level of depression than men. The psychometric scores were also differentiated by type of employment and job. Depression was identified in 44% of all the respondents. Conclusions: Individuals who are economically active during the pandemic report good quality of life and no or only mild signs of depression. Working people with higher education cope more effectively with adversities of the pandemic, compared to those with lower education. Int J Occup Med Environ Health. 2023;36(2):274–90