The role of perceived social support in the acculturation process of immigrants remains unclear. In this study, we jointly evaluated the associations between acculturative stress and negative emotions associated with discrimination as antecedents of anxiety, depression, and stress symptoms in 283 immigrants living in Chile. Three competing models were tested via structural equation modelling to assess (1) the association among these variables and mental health symptoms and (2) to clarify the role of perceived social support. The third model was theoretically more adequate, showed a better fit, and explained 42.7% of the variance of mental health symptoms. In this model, perceived social support was associated with acculturative stress by reducing mental health symptomatology. Moreover, a direct relationship and an indirect relationship were found between acculturative stress (through negative emotions associated with discrimination) and mental health symptomatology. These results contribute to the understanding of the acculturation process experienced by immigrants in Chile and provide empirical evidence to be used to improve migration policies. © 2022 by the authors.Universidad Católica de Temuco, UCT; Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT, (11181020); Agencia Nacional de Investigación y Desarrollo, ANID