Schizophrenia is one of the most severe chronic mental illnesses. It drastically changes an individual's life and well-being. Sexual well-being in schizophrenia is often sidelined, even though it is one of the main areas for maintaining quality of life. Based on the conservation of resources theory (COR) and empirical data, we assume that self-esteem and acceptance of illness help in coping with schizophrenia and maintaining sexual well-being. This pilot study aimed to determine the relationship between self-esteem, acceptance of illness, and sexual well-being in Polish individuals with schizophrenia. The results of 60 individuals were included in this study. In the present study, the Self-Esteem Scale (SES), Acceptance of Illness Scale (AIS), and Short Sexual Well-Being Scale (SSWBS) were used. The study showed a significant association between self-esteem, acceptance of illness, and sexual well-being. Self-esteem (β = 0.62) and acceptance of illness (β = 0.55) acted as positive and significant predictors of sexual well-being in individuals with schizophrenia. Acceptance of illness was also found to play a mediating role between self-esteem and sexual well-being in people with schizophrenia (indirect effect: β = 0.34; = 0.063; = 0.839). The current pilot study demonstrates the relationship between self-esteem, acceptance of illness, and sexual well-being. Our findings highlight the significant role of acceptance of illness in maintaining sexual well-being among individuals with schizophrenia.