Background: Spiritual well-being is crucial in human health and reduces anxiety and depression. Therefore, identifying its underlying variables can improve individuals’ health. Objectives: This study aimed to predict a model of spiritual well-being based on belief in a just world mediated by positive and negative effects in university students of Tehran. Methods: This was a descriptive correlation study performed through path analysis. The statistical population consisted of students studying at different universities of Tehran during 2020 - 2021. The research sample comprised 301 university students (199 female and 102 male). The participants completed the Spiritual Well-Being Scale, Belief in a Just World Scale, and Positive and Negative Affect Schedule (PANAS). The model was evaluated using path analysis in AMOS 24.0. Results: The results showed that the path coefficient between positive affect and spiritual well-being was positive and significant, and the path coefficient between negative affect and spiritual well-being was negative and significant (P < 0.001). The total path coefficient between the belief in a just world (BJW) and spiritual well-being was positive and significant, and the path coefficient between the belief in an unjust world (BUW) and spiritual well-being was negative and significant (P < 0.001). Furthermore, there was a significant positive indirect path coefficient between BJW and spiritual well-being (P < 0.001). Accordingly, the positive and negative affects played positive mediating roles between BJW and spiritual well-being. Conclusions: Based on the findings of the present study, it can be concluded that BJW, positive effects, and strengthening them can enhance the level of spiritual well-being and reduce the students’ negative effect, anxiety, and depression levels.