The present study examined the psychological effects and identify factors associated with worse outcomes, during the COVID-19 outbreak in Mexican nurses involved in fighting against COVID-19. An anonymous online questionnaire was applied through an online survey, which collected information regarding basic information, traumatic distress response (IES-R scale), emotional exhaustion (MBI-EE) and psychological distress (K10 scale). Results showed that 46.72% nurses reported moderate-severe traumatic distress response, 42.40% nurses evidenced a high level of emotional exhaustion and 41.78% showed moderate-severe psychological distress. Nurses who have >2 children, an increase in working hours due to COVID-19, tobacco and alcohol consumption and the increase in the consumption of the both and presence of a confirmed and suspected case of COVID-19 in their workplace showed worse outcomes. These findings demonstrate that a large portion of nurses in Mexico is suffering from psychological disturbances due to COVID-19 outbreak. In the face of a health crisis, not seen in several years in Mexico, the proper psychological well-being of the nurse’s staff at this vulnerable time is essential.