Objectives: In the current study, we aimed to evaluate the prognostic value of measuring C-reactive protein (CRP), procalcitonin (PCT), and mid-regional proadrenomedullin (MRProADM) at 2-time points (i.e., day 1 and day 5) in predicting 28-day mortality. Design: This was a cohort, cross-sectional study. Setting: In Zagazig University Hospitals from June 2019 to June 2020 as a collaboration between Clinical Pathology Department and the Intensive Care Unit. Patients and participants: The study included 32 septic intensive care unit (ICU) patients. Measurements and results: Blood samples (for serum separation) were collected from each patient on the first day of sepsis diagnosis (day 1) and then 5 days later (day 5). The serum was analyzed for CRP, PCT, and MR-ProADM. At the end of 28 days of observation, patients were classified as survivors or non-survivors. Comparing the level of each biomarker between survivors and non-survivors on day 1 and day 5 showed that only MR-ProADM was significantly different between groups at both measuring points. Meanwhile, PCT showed a significant difference only on day 5. On day 1, using 245.9 pg/ml as a cutoff point, MR-ProADM had 75% sensitivity and 85.7% specificity. Meanwhile on day 5, using 124.4 pg/ml as the cutoff for MR-ProADM, it had 80% sensitivity and 85.2% specificity. Conclusion: Based upon our findings in our study setting, MR-ProADM was a good mortality predictor for ICU patients with sepsis on both the first and fifth day of sepsis detection.