In this article, we induced acute changes in extracellular volume fraction in skeletal muscle tissue and compared the sensitivity of a standard 1H T2 imaging method with different 23Na‐NMR spectroscopy parameters within acquisition times compatible with clinical investigations. First, we analyzed the effect of a short ischemia on the sodium distribution in the skeletal muscle. Then, the lower leg of 21 healthy volunteers was scanned under different vascular filling conditions (vascular draining, filling, and normal condition) expected to modify exclusively the extracellular volume. The first experiment showed no change in the total sodium content during a 15 min ischemia, but the intracellular weighted 23Na signal slowly decreased. For the second part, significant variations of total sodium content, sodium distribution, and T1 and T2∗ of 23Na signal were observed between different vascular filling conditions. The measured sodium distribution correlates significantly with sodium T1 and with the short and long T2∗ fractions. In contrast, significant changes in the proton T2w signal were observed only in three muscles. Altogether, the mean T2w signal intensity of all muscles as well as their mean T2 did not vary significantly with the extracellular volume changes. In conclusion, at the expense of giving up spatial resolution, the proposed 23Na spectroscopic method proved to be more sensitive than standard 1H T2 approach to monitor acute extracellular compartment changes within muscle tissue.