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Abstract Background Although the relationship between cultural beliefs and schizophrenia has received some attention, relatively little work has emerged from African contexts. In this study we draw from a sample of South African Xhosa people with schizophrenia, exploring their cultural beliefs and explanations of illness. The purpose of the article is to examine the relationship between this cultural context and the content of delusions. Methods A sample comprising 200 Xhosa people with schizophrenia participating in a South African schizophrenia genomics study were interviewed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Participant delusions were thematically analyzed for recurring themes. Results The majority of participants ( n = 125 72.5%) believed that others had bewitched them in order to bring about their mental illness, because they were in some way jealous of the participant. This explanation aligns well with the understanding of jealousy-induced witchcraft in Southern African communities and highlights the important role that culture plays in their content of delusions. Conclusions Improved knowledge of these explanatory frameworks highlights the potential value of culturally sensitive assessment tools and stigma interventions in patient recovery. Furthermore such qualitative analyses contribute towards discussion about aspects of delusional thought that may be more universally stable, and those that may be more culturally variable.