Background: Self-management behaviors can reduce the progression of an illness. Although various factors affect self-management, no study has been conducted on the self-management of tuberculosis (TB) through path analysis.Objectives: This study evaluated the factors affecting self-management in TB patients using path analysis. Methods: A cross-sectional study was done on 133 non-prisoner TB patients that referred to all health centers in Karaj, Iran, in 2017. A structured questionnaire was applied. Data were analyzed with SPSS-17 and Lisrel 8.8, utilizing statistical path analysis to evaluate the relationships between self-management and its related factors. Results: Overall, 52.3% of the participants in the study were female and 47.7% were male. Respondents of were 46.9% smear-positive, 9.4% smear-negative, and 43.8% extra-pulmonary TB. Fit indices confirmed the model fitness and logical relationships between the variables according to the conceptual model (χ 2 = 49.80, df = 25). The final path model showed that age (β = 0.84), attitude (β = 0.10), marital status (β = 0.04), and house condition (β = 0.03) impact self-management through the direct path. Knowledge (β = 0.83) and education (β = 0.16) affect self-management through both direct and indirect paths. Education indirectly affects self-management through both knowledge and attitude. Knowledge indirectly impacts self-management through attitude. In other words, knowledge and attitude mediate the relationship between some factors and self-management. Conclusions: This study provided an empirical model that illustrates the relationships between self-management and related factors in TB patients. The knowledge can be the target of interventions in support of self-management.