Aim of the study: To evaluate the sonoelastic response of the median nerve in patients with carpal tunnel syndrome following conservative rehabilitation with splint plus exercise regimens. Materials and methods: A total of thirty-five patients diagnosed with mild carpal tunnel syndrome and treated with splint plus exercise therapy; hand resting splint all day for 3 weeks and then only at nights along with nerve gliding exercises in 10 repetitions 3 times a day. The median nerve was evaluated clinically prior to the treatment and at week 6 of therapy using physical examination, electrodiagnostic neurophysiology tests and radiological imaging; Boston Scores, electromyogram, ultrasonography and sonoelastography. Results: Following the 6-week treatment protocol on 35 subjects with mild carpal tunnel syndrome, sonoelastography showed significantly softer median nerve, while the traditional parameters based on Boston Scores and cross-sectional area based on ultrasonography remained nearly unresponsive. Such early indication of biomechanical changes in the nerve may be of clinical importance if it can offer a prognostic value of the applied treatment, while tissue softening suggests the alleviation of nerve compression. Conclusions: Sonoelasticity of the median nerve can serve as a reliable marker for assessing therapeutic changes in median nerve stiffness and potentially the outcome early on in mild carpal tunnel syndrome.