BackgroundGut damage allows translocation of bacterial lipopolysaccharide (LPS) and fungal β-D-glucan (BDG) into the blood. This microbial translocation contributes to systemic inflammation and risk of non-AIDS comorbidities in people living with HIV, including those receiving antiretroviral therapy (ART). We assessed whether markers of gut damage and microbial translocation were associated with cognition in ART-treated PLWH.MethodsEighty ART-treated men living with HIV from the Positive Brain Health Now Canadian cohort were included. Brief cognitive ability measure (B-CAM) and 20-item patient deficit questionnaire (PDQ) were administered to all participants. Three groups were selected based on their B-CAM levels. We excluded participants who received proton pump inhibitors or antiacids in the past 3 months. Cannabis users were also excluded. Plasma levels of intestinal fatty acid binding protein (I-FABP), regenerating islet-derived protein 3 α (REG3α), and lipopolysaccharides (LPS = were quantified by ELISA, while 1–3-β-D-glucan BDG) levels were assessed using the Fungitell assay. Univariable, multivariable, and splines analyses were performed.ResultsPlasma levels of I-FABP, REG3α, LPS and BDG were not different between groups of low, intermediate and high B-CAM levels. However, LPS and REG3α levels were higher in participants with PDQ higher than the median.Multivariable analyses showed that LPS association with PDQ, but not B-CAM, was independent of age and level of education. I-FABP, REG3α, and BDG levels were not associated with B-CAM nor PDQ levels in multivariable analyses.ConclusionIn this well characterized cohort of ART-treated men living with HIV, bacterial but not fungal translocation was associated with presence of cognitive difficulties. These results need replication in larger samples.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12981-023-00525-z.