Background: The relationship between emotional intelligence (EI) and stress has been widely studied, as well as the beneficial role of self-care to maintain health and wellbeing. However, the joint contribution of EI and self- care in predicting stress has not been examined during COVID-19 lockdown. This study aimed to examine the mediating role of self-care in the relationship between EI and stress and the potential moderator role of gender. Methods: A sample of 1082 participants from four Hispanic countries completed measures related to socio- demographic, trait emotional intelligence (Trait Meta-Mood Scale), self-care activities (Self-care Activities Screening Scale) and stress (Perceived Stress Scale). Results: Mediation analyses revealed that self-care increased the explained variance of the prediction of stress by EI dimensions after controlling gender and age. However, gender only moderated the relationship between selfcare and stress in the mediation model corresponding to emotional attention. Conclusions: Data supported a general model for the interaction of EI and self-care as contributing factors of stress. Further research is needed to replicate it in more culturally distant samples and to fully explore the po- tential role of gender differences. Future intervention programs should include a balanced combination of EI and self-care to increase their benefits on people’s health