2020 The Author(s). Background: Chronic Obstructive Pulmonary Disease (COPD) is a progressive and debilitating condition that affects individuals' quality of life. COPD self-management and supports provided by carers is key to the quality of life people living with COPD. Health literacy (HL) and Patient Activation (PA) are main drivers of self-management practices (SMPs). However, their contribution remains to be fully explored. This study aimed to examine the level of self-management practices, and the relationship with socio-demographic factors, HL and PA among multi-morbid COPD patients from rural Nepal. Methods: This is a cross-sectional study conducted between July 2018 and January 2019. Patients completed a survey, including Self-management Practices questionnaire (SMPQ), five domains of the Health Literacy Questionnaire (HLQ), and Patient Activation Measure (PAM). The relationship between HL, PAM, and SMPs was examined using univariate statistics. Multivariable analysis was conducted to identify the factors associated with SMPs. Results: A total of 238 patients responded to the study. The mean score of SMPQ was 45.31(SD = 9.00). The HLQ and PAM scores were positively correlated with the total score of SMPQ. Low level of SMPs were found to be positively associated with being uneducated (β = - 0.43, p =.001), having a low family income (β = - 5.22, p =.002), and, negatively associated with the presence of more than one co-morbidity (β = 3.58, p = 0.007) after controlling for other socio-demographic variables in the multivariable analysis. Conclusion: The overall SMPs among this sample of Nepalese with COPD were low. Our findings highlight the need to implement a self-management intervention program involving patient activation and health literacy-focused activities for COPD, creating a support system for patients from low-income families and low education.