Background: Health care workers (HCW) with post-COVID condition (PCC) are frequently reported to suffer from mental health impairment. Given HCW above-average risk for mental health, research is necessary and risk factors need to be assessed. Aim: To compare mental health and health of German HCW with and without PCC and to identify associated psychological and social factors. Design: Cross-sectional study. Method: Overall, 2816 German HCW participated (332 reported PCC). Measures were post-COVID condition symptom sum score (PCSS), symptoms of depression (Patient Health Questionnaire-2), anxiety (Generalised Anxiety Disorder-2) and post-traumatic stress disorder (PTSD) symptoms (Impact of Event Scale-6), work–family conflict (Work–Family Conflict Scale), social support (ENRICHD Social Support Inventory), sense of coherence (Sense Of Coherence-3 Scale) and working conditions. Group differences of HCW with and without PCC were investigated. Multiple linear regression analysis was performed for HCW with PCC. PCSS was the dependent variable. Independent variables were a.m. measures and age, gender, occupational group and migration background. Results: HCW with PCC exhibited higher values, with medium effect sizes, for symptoms of depression, anxiety and PTSD. Small effect sizes were observed for work–family conflict, social support, sense of coherence and working conditions. Higher PCSS scores were associated with higher depression, anxiety, PTSD and work–family conflict levels, lower social support and sense of coherence and migration background. Being a physician was associated with lower PCSS. Conclusion: Lower mental health, social factors and resources may play a role in reporting severe post-COVID symptoms. Further research is necessary to investigate these interactions using the biopsychosocial theory. Implication for the Profession: This study can help to understand PCC in HCW to design adjusted treatments and protect HCW from PCC and minimise their risk of PCC. Reporting Method: This study complies with the Journal article reporting standards for quantitative research in psychology: The APA Publications and Communications Board task force report (Data S1). Public Contribution: Caregivers are the sample group.