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Objective To explore the moderating and mediating role(s) of learning within the relationship between sense of coherence (SOC) and generalized resistance resources. Method Cross-sectional study (N = 481), using a self-administered questionnaire, of employees working in the healthcare sector in the Netherlands in 2017. Four residential healthcare settings and one healthcare-related Facebook group were involved. Multiple linear regression models were used to test for moderating and mediating effects of learning. Results Social relations, task significance, and job control significantly explained variance in SOC. Conceptual, social, and instrumental learning, combined, moderated the relationship between SOC and task significance. Instrumental learning moderated the relationship between job control and SOC. Social learning also mediated this relationship. Conceptual learning did not show any moderating or mediating effect. Conclusions The relationship between SOC and the three GRRs seems to be strengthened or explained −to a certain extent − by instrumental and social learning. Healthcare organizations are recommended to promote learning through formal activities as well as through cooperation, feedback, sharing experiences, and job challenges. This requires employee participation and a multilevel interdisciplinary approach.