Background: Sepsis is a life-threatening condition in ICU with high morbidity and mortality. Biomarkers which can act as a predictor for diagnosis, prognosis, and patient outcome in sepsis are needed. Aim: Aim of the study is to compare the significance of hs-C-reactive Protein (CRP), Procalcitonin, White blood cell count, and blood culture in patients with bloodstream infections and compare their prognostic significance with blood cultures in sepsis. Materials and Methods: This hospital based prospective observational study was conducted between July 2018 to July 2019 for one year with 216 cases of sepsis. Serial determination of Procalcitonin and CRP at admission and Day 6 was done. Data was analyzed check to compare the prognostic significance of the PCT, CRP, and WBC count. Results: A blood culture positivity rate of 50.9% was reported with male preponderance. WBC count has significantly reduced after 72hrs of admission (p= 0.007). CRP levels have significantly reduced on day 6 (p = 0.043) in comparison to at the time of admission (p= 0.032). The serial determination of PCT levels at admission and on day 6 (p= 0.032) was found to be a better prognostic indicator in patients with sepsis than at the time of admission. The significant patient outcome in terms of mortality and reduction in length of hospital stay has been found (p= 0.018, p=0.002). The positive correlation of PCT and CRP and SOFA score has been reported. Conclusion: Prognostic significance was found for the biomarkers PCT, CRP, and WBC count with significant patient outcomes in terms of mortality and hospital stay reduction.