Humour is considered as a crucial job resource for healthcare professionals. It has been further credited for several positive outcomes such as resilience and well-being. This study investigated: (a) the mediating role of resilience between adaptive humours styles (self-enhancing and affiliative) and well-being at work and (b) the moderating role of self-esteem in the indirect relationship between the adaptive humour styles and well-being at work via resilience. The study was conducted on a sample of 354 healthcare professionals. The findings of the study indicate a significant association between the adaptive humour styles and well-being at work with resilience as a mediator. Furthermore, self-esteem was found to significantly moderate the indirect relationship between self-enhancing humour and well-being at work via resilience.