Concurrent resistance and aerobic exercise (CE) is recommended to ageing populations, though is postulated to induce diminished acute molecular responses. Given that contraction-induced cytokine mRNA expression reportedly mediates remunerative postexercise molecular responses, it is necessary to determine whether cytokine mRNA expression may be diminished after CE. Eight middle-aged men (age, 53.3 ±1.8 years; body mass index, 29.4 ± 1.4 kg·m−2) randomly completed (balanced for completion order) 8 × 8 leg extensions at 70% maximal strength (RE), 40 min of cycling at 55% of peak aerobic workload (AE), or (workload-matched) 50% RE and 50% AE (CE). Muscle (vastus lateralis) was obtained pre-exercise, and at 1 h and 4 h postexercise, and analyzed for changes of glycogen concentration, tumor necrosis factor (TNF), TNF receptor-1 and -2 (TNF-R1 and TNF-R2, respectively), interleukin (IL)-6, IL-6R, IL-1, and IL-1 receptor-antagonist (IL-1ra). All exercise modes upregulated cytokine mRNA expression at 1 h postexercise comparably (TNF, TNF-R1, TNF-R2, IL-1, IL-6) (p< 0.05). Expression remained elevated at 4 h after RE and AE (p < 0.05), though returned to pre-exercise levels after CE (p > 0.05). Moreover, AE and RE upregulated IL-1 and IL-1ra expression, whereas CE upregulated IL-1 expression only (p < 0.05). Only AE reduced muscle glycogen concentration (p < 0.05), whilst upregulating receptor expression the greatest; though, IL-6R expression remained unchanged after all modes (p > 0.05). In conclusion, in middle-aged men, all modes induced commensurate cytokine mRNA expression at 1 h postexercise; however, only CE resulted in ameliorated expression at 4 h postexercise. Whether the RE or AE components of CE are independently or cumulatively sufficient to upregulate cytokine responses, or whether they collectively inhibit cytokine mRNA expression, remains to be determined.