OBJECTIVE: The objective of this study is to analyse the relationship and psychosocial issues between working during the COVID-19 pandemic in primary healthcare (PHC) facilities located in the most vulnerable health region (HR) of the Federal District of Brazil (FDB) compared with a lesser region. DESIGN: Mixed-method study data. The questionnaire was based on the World Health Survey and the Convid Behavioural Survey. Quantitative data were described in absolute and relative frequency. Pearson's χ2 test verified differences according to the region (significance level <5%). A margin of error of 8% with 95% CI defined the sample. The content analysis (by Bardin) analysed the qualitative data. SETTING: A representative sample of PHC professionals working at the Western HR and Central HR of the FDB. PARTICIPANTS: 111 women and 27 male PHC professionals, aged ≥ 18 years. OUTCOME MEASURES: Psychosocial variables-personal emotions towards the clients, social relationships and use of psychoactive substances (PAS). INTERVENTION: An online questionnaire (27 questions) and 1 open-ended question. RESULTS: The sample comprised 138 PHC professionals; 80.40% were female aged between 40 and 49 years old (27.3%); declared themselves as black/pardo (58.7%); were married (53.60%), and worked in family healthcare teams (47.80%). No association between working in the most vulnerable HR compared with the least one and presenting psychosocial issues, except for anger towards clients (p=0.043). 55.10% worked much more than usual, 60.80% reported being depressed, 78.20% anxious, 76.80% stressed, 77.50% had no empathy and 78.30% felt isolated from family/friends. Towards the clients, 59.40% reported empathy and 72.5% no affection/care. The consume of psychotropic medications was reported by 34.80%, and 14.50% increased alcohol/PAS use. Qualitative data leverage quantitative findings: work overload, the indifference of the Federal Government and distance from family/friends. CONCLUSION: Working in the most vulnerable region and in the least one affects the psychosocial aspects of the PHC professionals equally.