Neutrophil-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelets-lymphocyte ratio (PLR) are biomarkers easy-to-obtain and could be used in clinical practice to verify an inflammatory status and are associated with alcohol use disorder (AUD) and cocaine use disorder (CUD). Our aim was to compare NLR, MLR and PLR among men with AUD and CUD and to assess the relationship between these biomarkers and addiction-related outcomes. This is a cross-sectional study comprising 979 inpatient men diagnosed with substance use disorder (391 with AUD and 588 with CUD) under hospital treatment for drug addiction. Individuals with AUD had higher NLR and MLR (p=0.041, p<0.001 respectively) compared to individuals with CUD. In the AUD group, positive correlations between age and MLR (r=0.111; p=0.029), NLR and liver enzymes ALT and AST (r=0.103, p=0.043; r=0.155, p=0.002; respectively), and MLR and ALT, AST and GGT levels were observed (r=0.173, p=0.001; r=0.242, p<0.001; r=0.167, p=0.001, respectively). Individuals with CUD showed a positive correlation between age and NLR (r=0.113; p=0.006). The presence of clinical comorbidities, HIV, HCV and syphilis were not associated with NLR, MLR, and PLR (p>0.05). These biomarkers are a rapid and inexpensive way to assess the effects of substance use on the inflammatory profile. Our findings contribute with valuable insights into the distinctive inflammatory profiles associated with AUD and CUD. These insights could guide further research and the development of more studies, which could include control groups, in order to refine the clinical applicability of these biomarkers.