Self-esteem appears to play a central role in the spiritual life and ethical behaviour of the typical Iranian. For example, for many Iranians, humankind is believed to be the crown of creation, and each person is believed to be individually valued by God. Previous empirical studies also indicate that in Iran spirituality is positively associated with self-esteem. On this basis, it was hypothesised that self-esteem would be one of the mechanisms through which spirituality leads to increased mental well-being. Mediation analysis showed that self-esteem was a partial mediator of the spirituality–well-being relationship. Moreover, results of moderated mediation analysis revealed that this mediation was not significantly moderated by gender, and that the indirect path through self-esteem was significant in both genders. Implications of the results and their relevance to other western and eastern religions (e.g. Christianity and Buddhism) are discussed.