The goal of the study was to determine the effects of continuous (CT) vs. intermittent (IT) training yielding identical mechanical work and training duration on skeletal muscle and cardiorespiratory adaptations in sedentary subjects. Eleven subjects (6 men and 5 women, 45±3 years) were randomly assigned to two periods of 24 trainings sessions over 8 weeks in a cross-over design, separated by 12 weeks of detraining. Maximal oxygen uptake (VO_2max) measured during maximal exercise testing increased after both trainings (9% with CT vs. 15% with IT), whereas only IT was associated with faster VO₂ kinetics (: 68.0±1.6 vs. 54.9±0.7 sec, p<0.05) measured during a test to exhaustion (TTE) and with improvements in maximal cardiac output (Q_max, from 18.1±1.1 to 20.1±1.2 L·min^-1, p<0.01). Skeletal muscle mitochondrial oxidative capacities (V_max) were only increased after IT (3.3±0.4 before and 4.5±0.6 µmol O2·min^-1·gdw^-1 after training, p<0.05) whereas capillary density increased after both trainings, with a 2-fold higher enhancement after CT (+21±1% for IT and +40±3% after CT, p<0.05). The gain of V_max was correlated with the gain of TTE and the gain of VO_2max with IT. The Gain of Q_max was also correlated with the gain of VO_2max. These results suggest that fluctuations of workload and oxygen uptake during training sessions, rather than exercise duration or global energy expenditure, are key factor in improving muscle oxidative capacities. In an integrative view, IT seems optimal in maximizing peripheral muscle and central cardiorespiratory adaptations, permitting significant functional improvement. These data support the symmorphosis concept in sedentary subjects.