Background <p>Disease-related inflammation affects chemosensory signaling, but knowledge on the impact of exercise-induced low-grade inflammation on taste function remains scarce. Here we hypothesized that intense habitual physical activity modifies sweet taste perception via increased cytokine release.</p> Methods <p>In an observational human study we compared participants (m/f) engaging in high (<i>n</i> = 34) and low (<i>n</i> = 31) levels of habitual physical activity. Salivary IL-6 and urinary 8-iso-prostaglandin F2α levels, body composition, sucrose recognition threshold, preference and consumption of sweet foods, size and area of fungiform papillae as well as selected hormones regulating food intake were recorded. Statistical analysis was conducted using Principal Component Analysis (PCA) followed by Student’s t-tests and multiple regression models.</p> Results <p>The PCA summarized the main outcome variables to two principal components (PC). PC1 was primarily influenced by body composition and fungiform papillae markers, while sucrose recognition thresholds, sweet food consumption, and IL-6 levels strongly contributed to PC2. Compared to the low activity group, the high activity group showed on average an increased sucrose recognition threshold (+ 35.8 ± 12.8%), increased IL-6 concentrations (+ 25.6 ± 10.9%), higher consumptions of sweet foods (+ 18.8 ± 4.9%) and decreased number (­24.8 ± 4.9%) and area (-29.8 ± 6.4%) of fungiform papillae.</p> Conclusions <p>The association between modified sweet taste function markers and increased IL-6 levels suggests that inflammatory processes may contribute to exercise-related changes in chemosensory perception.</p> Trial registration <p>The study was approved by the Ethics Committee of the University of Vienna (approval number 01125) and registered at ClinicalTrial.gov (NCT06384365).</p> Graphical abstract <p></p>