Abstract Background Monocyte distribution width (MDW) is an immune response biomarker and part of a CBC differential. MDW is derived from the distribution of monocyte volumes and elevated MDW values correlate with severe infections and sepsis in Emergency Department (ED) adult patients. Neutrophil to lymphocyte ratio (NLR) is predictive of infections and inflammatory stress. Evaluating these biomarkers could be valuable in bacteremia risk assessment. Bacteremia is the presence of viable bacteria in the bloodstream and is present in up to 20% of septic patients. Blood cultures establish pathogen identity but require culture time, potentially delaying appropriate treatment. Our goal was to characterize MDW and NLR clinical performance in ED patients with suspected bacteremia. Methods This was an observational cohort study of ED patients 18 years and older with CBC differential and blood cultures obtained. MDW values ≥20 is the published cut-off for increased infection risk. Clinical literature suggests that NLR ≥3 is abnormal. We assessed the diagnostic performance of MDW and NLR for positive blood cultures using SPSS Version 25. Results From 07/2021-09/2023, 9,400 blood cultures were ordered and 5174 patients had differential CBCs. The overall blood culture positivity rate was 14.4%. MDW and NLR performance for positive blood cultures is shown in Table 1. Conclusions Our analysis provides evidence that MDW and NLR may be useful for early recognition of bacteremia in ED patients. CBC differential results are reported sooner than culture results. MDW is directly reported, NLR can be readily calculated from the differential. Therefore both could contribute to earlier risk stratification and our findings suggest potentially distinct information from MDW and NLR. Combining MDW with other CBC parameters may provide additional diagnostic advantage. Further analysis will incorporate added clinical data for enhanced decision support in interpreting MDW values in the context of pending blood culture results.