Background. Pneumonia substantially kills children aged 2–59 months in South Sudan. However, information on health workers adherence to Integrated Management of Childhood Illnesses (IMCI) guideline in treating children with cough/difficulty in breathing remains scarce. This study assessed factors associated with adherence to IMCI guideline in Aweil East County, South Sudan. Methods. This cross-sectional study involved 232 health workers from 36 health facilities. Data collected using structured questionnaire and checklist was double-entered in EpiData and analyzed with STATA at 5% significance level using logistic regression. Results. Respondents mean age was 32.41±7.0 years, 154 (66.4%) were males, 104 (44.8%) reached secondary education, and 190 (81.9%) had certificate. 23 (9.9%, 95% CI: 6.4–14.5) adhered to IMCI guideline. Holding diploma (adjusted odds ratio (AOR) = 6.97; 95% Confidence Interval (CI): 1.82–26.67; P=0.005), shorter time to follow guideline steps (AOR = 12.0; 95% CI: 2.73–61.66; P<0.001), and nondifficult use (AOR = 27.7; 95% CI: 5.40–142.25; P<0.001) were associated with adherence. Conclusion. Adherence was low. Academic qualifications, guideline complexity, and availability of IMCI drugs were associated factors.