Aim This study assessed and compared acute muscle molecular responses before and after 5‐week training, employing either aerobic (AE) and resistance exercise (RE) or RE only. Methods Ten men performed one‐legged RE, while the contralateral limb performed AE followed by RE 6 h later (AE+RE). Before (untrained) and after (trained) the intervention, acute bouts of RE were performed with or without preceding AE. Biopsies were obtained from m. vastus lateralis of each leg pre‐ and 3 h post‐RE to determine mRNA levels of VEGF, PGC‐1α, MuRF‐1, atrogin‐1, myostatin and phosphorylation of mTOR, p70S6K, rpS6 and eEF2. Results PGC‐1α and VEGF expression increased (P < 0.05) after acute RE in the untrained, but not the trained state. These markers showed greater response after AE+RE than RE in either condition. Myostatin was lower after AE+RE than RE, both before and after training. AE+RE showed higher MuRF‐1 and atrogin‐1 expression than RE in the untrained, not the trained state. Exercise increased (P < 0.05) p70S6K phosphorylation both before and after training, yet this increase tended to be more prominent for AE+RE than RE before training. Phosphorylation of p70S6K was greater in trained muscle. Changes in these markers did not correlate with exercise‐induced alterations in strength or muscle size. Conclusion Concurrent exercise in untrained skeletal muscle prompts global molecular responses consistent with resulting whole muscle adaptations. Yet, training blunts the more robust anabolic response shown after AE+RE compared with RE. This study challenges the concept that single molecular markers could predict training‐induced changes in muscle size or strength.