Background: The most frequent subtype of Non-Hodgkin Lymphoma (NHL) is diffuse large B cell lymphoma (DLBCL), which accounts for 25% to 30% of cases. The mean platelet volume (MPV) indicates the size, function, and activity of platelets in circulation. Red cell distribution width (RDW) is regarded an inflammatory related marker, both indicators are potential predictors of overall mortality in a variety of cancers. Objective: This study aimed to find out the association between MPV and RDW with disease free survival (DFS) in adults with DLBCL. Patients and methods: This observational retrospective study was conducted on 112 patients of a total of 140 DLBCL patients who achieved CR after receiving R-CHOP protocol to clarify the association of MPV and RDW with 2-year DFS outcome in a cohort of adults diagnosed as de novo DLBCL (NOS) who were treated at The Haematology Units of International Medical Centre, Zagazig and Menoufia University Hospitals. Results: A total of 140 patients with DLBCL were observed in this study of which 112 patients achieved CR after receiving R-CHOP protocol the remaining who didn't achieve CR were ruled out. The mean age for those 112 patients was 53.12 years and 70 (62.5%) were males. The cut-off value for detecting DFS in MPV was 9.1 with 82.6% sensitivity and 59.1% specificity (P < 0.001) indicating better DFS in DLBCL patients with higher MPV. The cut-off value for detecting DFS in RDW was 14.1 with 77% sensitivity and 63% specificity (P=0.041) indicating better DFS in DLBCL patients with lower RDW. Conclusion: Lower baseline MPV values, and higher baseline RDW values were associated with inferior DFS outcome in patients with Denovo DLBCL after achieving CR upon receiving standard R-CHOP protocol.