Background: Impaired Health related quality of life (HRQOL) after women's childbirth affects women in a wide range of ways including limiting their daily activity, reducing self-care capacity, impairing childcare including effective breastfeeding and baby weaning, and increasing the cost of medical care, both for women and for their newborn babies. This study aimed to assess the HRQOL and its predictors among postpartum women in Southeast Ethiopia. Methods: Between March and May 2022, an institutional-based cross-sectional study was conducted among a simply randomly selected sample of 794 postpartum women who were attending immunization services in public health facilities in Southeast Ethiopia. The pretested interviewer-administered structured, Short Form 36 (SF-36), validated questionnaire was used to collect data and to assess the HRQOL. This Descriptive statistics were computed and the bivariable and multivariable logistic regression model was fitted to predictors of HRQOL. Odds ratio (OR), along with a 95% confidence interval (CI), were used to estimate the strength of the associations. Results: The mean scores (mean ± SD) of overall HRQOL, physical component summary (PCS) and mental component summary (MCS) of quality of life were 43.80 ± 27.88, 45.39 ± 28.58 and 42.20 ± 28.15) respectively. Walking to the health facility [(AOR = 2.09; 95% CI: (1.31,3.31)], using public transport (AOR=2.58; 95% CI=1.69–3.93), giving birth to ≤ 3 deliveries (AOR = 1.81; 95% CI: 1.36 –2.65), having health facility admission history during the recent baby’s pregnancy (AOR=1.62; 95% CI=1.08–2.44), having postpartum depression (PPD) (AOR=2.13; 95% CI=1.57–2.89) and having the fear of COVID-19 (AOR=1.46; 95% CI=1.08–1.99) were predictors of a lower level of HRQOL among postpartum women. Conclusion: This study revealed that nearly half of the postpartum women had a lower HRQOL. Means of transport used, the number of total deliveries they had, admission history during the recent baby pregnancy, PPD and Fear of COVID 19 (FCV 19) showed a statistically significant association with the lower overall HRQOL. To improve the HRQOL among postpartum women in Ethiopia, programs should be implemented by applying appropriate strategies that address the identified factors.