: Individuals diagnosed with substance use disorders (SUD) exhibit notable deficits in executive function (EFs). Notably, the pro-inflammatory cytokine interleukin-6 (IL-6) has been associated with cognitive impairments in individuals with substance use disorders. The specific neuropsychological parameters most affected by executive dysfunction remain poorly understood. : In this study, sixteen patients diagnosed with SUD in the withdrawal phase were compared to twenty age-matched control subjects to ascertain which aspects of EFs were most adversely impacted. Plasma levels of IL-6 were quantified using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using the Confidence Interval-Based Estimation of Relevance (CIBER) model to determine the most sensitive executive performance indicators. : Findings from the CIBER analysis revealed that the Wisconsin Card Sorting Test yielded the most pronounced cognitive discrepancies between males with and without SUD diagnoses. Elevated levels of IL-6 and associated executive dysfunction were observed to persist in males with SUD throughout the withdrawal phase. : Notably, cognitive flexibility emerged as the most sensitive parameter indicative of executive dysfunction, suggesting its potential utility in tailoring clinical interventions for SUD patients during this critical recovery period.