Background: Due to their debilitating and progressive conditions, chronic obstructive pulmonary diseases (COPD) can reduce patients' quality of life (QOL) and cause fatigue. This study aimed to compare the effect of telephone and SMS follow-up of an empowerment program on QOL and fatigue in patients with COPD.Methods: This non blind randomized clinical trial (RCT) study was conducted on 105 patients with COPD in 2016-2017 in Shahrekord city. First, the pulmonary empowerment program was implemented for six 90-min sessions. Then, the patients were randomly assigned to three control, telephone follow-up, and SMS follow-up groups (35 individuals in each group) using a random number table. Data were collected in the first and the sixth sessions of the empowerment program and at the end of the follow-up period by demographic, QOL, and fatigue questionnaires. Eventually, they were analyzed through correlation coefficient and analysis of variance (ANOVA) tests using SPSS software (Ver. 20).Results: The study results on QOL showed that the groups were not significantly different before and after the empowerment (p > 0.05). However, they were statistically significant differences were observed between the groups at the end of the quarterly follow-up period (p < 0.001). ANOVA results for fatigue indicated no statistically significant differences between the groups before and after the empowerment (p > 0.05). The three groups were not significantly different after the intervention (p = 0.05).Conclusion: Based on the results, it is recommended to utilize follow-up as an important principle in empowerment using various technology methods and design more comprehensive empowerment to reduce patient fatigue.Trial registration: Iran National Committee for Ethics in Biomedical Research (IR.SKUMS.REC.1398.104) and the Iranian Registry of Clinical Trials (IRCT20170122032101N4) (6/4/2020).