The importance of appraisal in the stress process is unquestioned. Experience in the social environment that impacts outcomes such as depression are thought to have these effects because they are appraised as a threat to the individual and overwhelm the individual’s capacity to cope. In terms of the nature of social experience that is associated with depression, several recent studies have examined the impact of cultural consonance. Cultural consonance is the degree to which individuals, in their own beliefs and behaviors, approximate the prototypes for belief and behavior encoded in shared cultural models. Low cultural consonance is associated with more depressive symptoms both cross-sectionally and longitudinally. In this paper we ask the question: does perceived stress mediate the effects of cultural consonance on depression? Data are drawn from a longitudinal study of depressive symptoms in the urban community of Ribeirão Preto, Brazil. A sample of 210 individuals was followed for 2 years. Cultural consonance was assessed in four cultural domains, using a mixed-methods research design that integrated techniques of cultural domain analysis with social survey research. Perceived stress was measured with Cohen’s Perceived Stress Scale. When cultural consonance was examined separately for each domain, perceived stress partially mediated the impact of cultural consonance in family life and cultural consonance in lifestyle on depressive symptoms. When generalized cultural consonance (combining consonance in all four domains) was examined, there was no evidence of mediation. These results raise questions about how culturally salient experience rises to the level of conscious reflection.