Carnosine (Carn) has a pluripotent role in skeletal muscle (SkM) physiology, enhancing intracellular buffering, acting as an antioxidant, antiglycating and ion‐chelating agent, and also acts as a diffusible Ca2+/H+ exchanger. Carn role as an antioxidant may reduce apoptosis, but has not been fully investigated in human SkM. Therefore, the purpose of this study was to investigate if SkM Carn influences apoptotic signaling in response resistance exercise. Fourteen recreational active men completed a lower‐body resistance exercise protocol consisting of the squat, leg press, and leg extension exercises. Blood samples were obtained before (PRE), immediately‐(IP), one‐(1H), five‐(5H), 24‐(24H) & 48‐(48H) hours post‐resistance exercise. SkM biopsies were obtained from the vastus lateralis at BL, 1H, 5H, & 48H post‐resistance exercise. SkM carnosine content was assessed via HPLC. Participants were placed into either a high Carn (HI: n = 7; Carn = 12.25 ± 2.40 mmol·kg−1WW) or a low Carn (LO: n =7; Carn = 5.60 ± 1.27 mmol·kg−1WW) group for analysis. Multiplex signaling assay kits were used to quantify phosphorylation status of apoptotic markers (JNK, FADD, p53, BAD, Bcl‐2). Circulating measures of muscle damage [myoglobin (Mb)] and oxidative stress [8‐hydroxy‐2′ – deoxyguanosine (8OHdG)] were assessed via ELISA. To control for BL differences a repeated measures analysis of covariance was used to analyze SkM data. Area under the curve (AUC) analysis was determined by the trapezoidal method. Although no significant interactions between the groups were observed for FADD, BAD, p53, Mb, or 8‐OHdG (p > 0.05)in response to resistance exercise, significant interactions were observed for JNK (p = 0.019) and Bcl‐2 (p = 0.032). Post‐hoc analysis indicated a significantly greater response at 1H for HI compared to LO in JNK (p = 0.035), while a trend towards an increase (p = 0.065) was observed for Bcl‐2. In addition, changes in Bcl‐2 and JNK following exercise were only significant in HI (p = 0.009 and p = 0.007, respectively), but not LO (p = 0.370 and p = 0.369, respectively). AUC analysis for 8OHdG indicated that circulating concentrations for HI (6,107.5 ± 2,144.6 ng·mL−1·min−1) was significantly (p = 0.037, D = 1.25) less than LO (8,838.7 ± 2,222.3 ng·mL−1·min−1). In conclusion, our results indicated that participants with higher Carn have a reduction in pro‐apoptotic proteins, with an attenuated circulating oxidative stress response to exercise.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.