The COVID-19 pandemic has had an important negative psychological impact on people worldwide, especially nursing professionals who seem to be more vulnerable to the development of psychopathological symptoms. Objective: To analyze relationships between variables from the social and clinical contexts with psychopathological symptoms in nursing professionals from different geographic regions of Brazil during the COVID-19 pandemic. Methods: Cross-sectional study carried out with 1737 nursing professionals from the five regions of Brazil. Data collection was carried out online with a questionnaire made available via Google Forms containing sociodemographic, occupational, and clinical questions, and the Symptom Assessment Scale-40-R, for the assessment of psychopathological symptoms. Differences between mean scores for the severity of psychopathological symptoms were assessed using the Mann–Whitney and Kruskall–Wallis tests. Results: There was a significant difference in the psychoticism domain scores according to Brazilian geographic region, with greater severity among professionals from the North and Northeast regions when compared with those from the South region. Social context variables (gender, age group, and marital status) and clinical variables (psychological and psychiatric follow-up; psychological or emotional support by the institution; family member, friend, neighbor, or co-worker with COVID-19, and death among them; use of psychiatric medication without a medical prescription; and taking steps to take care of their mental health) were significantly related to psychopathological symptoms. Conclusions: The results point to the importance of mental health promotion strategies for professionals through psychological or emotional support, as evidence indicates that this support can be a predictor of reduced psychological distress.