Background: Community-acquired pneumonia (CAP) is one of the most common causes of death among children all over the world, The aim of the current study was to evaluate the mean platelet volume (MPV) and presepsin as diagnostic markers in childhood pneumonia and to estimate their reliability in assessing the severity of the disease. Subjects and methods: The study included 90 children who were distributed into three groups as follows, 30 healthy children as a control group, 30 cases with pneumonia and 30 cases with severe pneumonia. Full history, clinical examination and laboratory investigation (including measurement of serum presepsin and MPV) were conducted for every child. Results: The mean MPV in the control group was 7.94 ± 0.84 that was statistically significantly lower as compared with the cases with pneumonia (9.81 ± 0.97). Both groups had statistically significantly lower MPV as compared with the severe pneumonia group (10.7 ± 0.89) (p < 0.001). The mean presepsin level in the control group was 141.14 ± 71.4 that was statistically significantly lower as compared with the cases with pneumonia (605.80 ± 176.11). Both groups had statistically significantly lower MPV as compared with the severe pneumonia group (1276.72 ± 1061.64) (p < 0.001). AUC of presepsin and MPV in identifying cases with pneumonia was (0.963 and 0.912 respectively) while AUC of presepsin and MPV in identifying cases with severe pneumonia was (0.877 and 0.789 respectively). Conclusion: both serum presepsin and mean platelet volume (MPV) could be used as non-invasive biomarkers in diagnosis of pneumonia