Background <p>Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) have been linked to venous thromboembolism (VTE) across various cancer types; however, their relationship with diffuse large B-cell lymphoma (DLBCL) remains largely unexplored. This study aimed to investigate the role of these inflammatory markers in predicting the risk of VTE in patients with DLBCL.</p> Method <p>A retrospective cohort study was conducted to analyze NLR, PLR, and SII in 224 DLBCL patients prior to chemotherapy. Of them, 31 (13.8%) patients were diagnosed with VTE, while the remaining 193 patients were considered as the control group.</p> Results <p>The median age was 55 (30) years, with men representing 57% of the patients. The majority of VTE events occurred during active treatment (58%), however; 42% of VTE cases were diagnosed prior to the initiation of treatment. NLR, PLR, and SII were significantly higher in DLBCL patients who developed VTE compared with the control (<i>P</i> = 0.003, <i>P</i> = 0.015, and <i>P</i> = 0.027, respectively). The optimal cut-off values were &gt; 2.41 for NLR (<i>P</i> = 0.003, with a sensitivity of 68% and specificity of 63%), &gt; 185 for PLR (<i>P</i> = 0.016, with a sensitivity of 71% and specificity of 67%), and &gt; 656 for SII (<i>P</i> = 0.027, with a sensitivity of 64% and specificity of 55%). Area under the curve values were 66% for NLR, 63% for PLR, and 62% for SII. The multivariate logistic regression model showed that NLR (ORa 3.750, <i>P</i> = 0.001) and PLR (ORa 5.211, <i>P</i> &lt; 0.001) were independent predictors of VTE in DLBCL patients.</p> Conclusions <p>NLR and PLR could be beneficial predictors of potential VTE in DLBCL patients without additional costs to the healthcare systems.</p>