COVID-19 frontline healthcare workers (FHCW) are struggling to cope with challenges that threaten their wellbeing. We examine the frequency and predictors of the most frequent mental health problems (MHP) among FHCW during the first COVID-19 peak in Mexico, one of the most severely affected countries in terms of FHCW’s COVID-19 mortality. A cross-sectional survey was conducted between May 8 and August 18, 2020. A total of 47.5% of the sample (n = 2218) were FHCW. The most frequent MHP were insomnia, depression, posttraumatic stress symptoms, and health anxiety/somatization (whole sample: 45.7, 37.4, 33.9, and 21.3%; FHCW: 52.4, 43.4, 40.3 and 26.1, respectively). As compared to during the initial COVID-19 phase, depression and health anxiety/somatization symptoms as well as experiences of grieving due to COVID-19, personal COVID-19 status, and having relatives and close friends with COVID-19 were more frequent during the COVID-19 peak. Obesity, domestic violence, personal COVID-19 status, and grieving because of COVID-19 were included in regression models for main FHCW’s MHP during the COVID-19 peak. In conclusion, measures to decrease other country-level epidemics contributing to the likelihood of COVID-19 complications (obesity) and MHP (domestic violence) as well as FHCW´s probability of COVID-19 infection could safeguard not only their physical but also mental health.