Background: Good sibling relationships in adulthood are known to be a protective factor for mental health. The quality of these relationships is influence by the sibship's inherent characteristics (e.g., birth order, number of brothers and sisters, sex composition, age gaps). The present study explored whether these same determinants can help to explain how individuals experience their relationship with a sibling who has been diagnosed with schizophrenia. Method: A total of 374 adults completed the Adult Sibling Relationship Questionnaire, a scale that probes the quality of these relationships on three dimensions: warmth, conflict, and rivalry. We also collected sociodemographic data and information about family structure from each of the participants. Participants were divided into two matched groups: nonclinical sibling group (n = 187) or schizophrenia sibling group (n = 187). Regression analyses were conducted to extract possible predictors of sibling relationship quality for each group. Further regression analyses then focused exclusively on relationships with an ill sibling, in order to study the role of disease-related variables in explaining each of the three dimensions. Results: Results showed that sociodemographic and family structure data explained a significant proportion of variance in the sibling relationship, but solely for nonclinical siblings. When participants had a sibling with schizophrenia, we found that disease-related variables (symptom severity, frequency of treatment) also had to be included to predict the conflict dimension. Conclusions: Our results suggest that feelings of conflict experienced by the schizophrenia sibling group were fueled by the symptoms the ill person displayed. Healthy brothers and sisters probably have only a poor understanding of these symptoms. This could be improved by supporting them and helping them learn more about the disease. Future research will have to prove that providing such support for siblings does indeed improve the quality of their sibling relationships and, by so doing, enhance the wellbeing of both members of a sibling dyad.