Objectives: The present study focused on the relationship between occupational activity and mental health during the first COVID-19 lockdown. Material and Methods: At the turn of May and June 2020, an online survey was conducted on a representative sample of 3000 Poles (age: Me = 45 years). Working persons accounted for 52% of the respondents, while 38.1% were hired workers. Two standardized (0–100 pts) indices were defined. The level of mental health symptoms index (LMHSI) concerned the incidence of 4 problems within the past 2 months, whereas the change in mental health symptoms index (CMHSI) concerned the degree of mental health deterioration. Results: The mean value of LMHSI was 40.91 (SD = 26.97), and that of CMHSI 60.51 (SD = 23.97). In both cases, a worse assessment was obtained among women than among men. In the group of working respondents, the least advantageous results were found among those who worked casually or under a commission contract. Among the non-employed respondents, jobless persons and students were the group at risk. Remote work resulted in the deterioration of mental health in the light of CMHSI; however, a threat of changes in the professional situation affected LMHSI variability to the greatest extent The results of linear regression (R² = 0.339) suggest that the increase in the CMHSI score (adjusted for LMHSI) is independently influenced by female sex, university education, remote work and a threat of the worsening of employment terms. The analysis of the interaction effect showed a stronger impact of the last factor in the group of women (p = 0.001). Conclusions: To conclude, COVID-19 restrictions were associated with a negative impact on mental health which should be analyzed in the occupational context. Int J Occup Med Environ Health. 2021;34(2):251–62