Muscle injuries are, after the ligament sprains, the most frequent injury of soft tissues in athletes. The study of the Delayed Onset Muscle Soreness (DOMS) from an Eccentric Exercise Protocol (EEP) has been proved as a valuable experimental model, where the muscular damage is comparable to a clinical muscular injury. The main characteristics of DOMS are soreness, muscle injury and functional impairment, where the effects of therapeutic Ultrasound (US) and cryotherapy (CRY) are normally oriented. PURPOSE To determine if the combined therapy of US and CRY, after an EEP, is able to control the DOMS. METHODS Thirty seven healthy men and women were recruited for a simple-blind, placebo-controlled trial. Parameters as difference with the baseline Pain (dVAS) with a 20 grs/mm compression, mid arm relaxed girth (dMAG), maximal isometric voluntary contraction (dMIVC), and rest elbow angle (dREA) and Total Plasma Creatine Kinase activity (CK) were measured 72 hours before, immediately after, and 24, 48, 72, 96 and 168 hours after a 80% MIVC nondominant elbow flexors eccentric-exercise protocol. Subjects were randomly assigned in one of the follow groups: Control-Control (CON-CON) without EEP and any treatment (n=8), Control-Exercise (CON-EXC) with EEP and no kind of treatment (n=10), US sham+CRY (USC-S) with EEP and placebo US treatment plus CRY (n=10) and US+CRY (USC) with EEP and US treatment plus CRY. The CRY was a 20 minutes cold pack protocol applied immediately after, 12, 24, 36, 60, 84 and 108 hours after the EEP; while the US was applied by 10 minutes, 36, 60, 84 and 108 hours after the EEP, with a 0,04–0.16 W/cm2 variable SATA. RESULTS: No statistical differences (p > 0.05) were observed for any studied parameter at the within group CON-CON analysis, confirming the statistical baseline. CK levels were lower in USC group compared to CON-EXC group at 48 hours after EEP (356.73 ± 436.93 v/s 1402.80 ± 1491.81 U/L, p < 0.05) and higher in USC-S group compared to CON-CON group at 96 and 168 hours after EEP (1801.88 ± 1316.70 v/s 185.71 ±132.78 U/L, and 1449.88 ±1038.73 v/s 131.63 ± 57.22 U/L, p < 0.05, respectively), without statistical significances between USC and CON-CON groups at any time. At the dMAG, USC-S group were lower than USC group at 24 and 48 hours after EEP (−0.08 ± 0.39 v/s 0.54 ± 0.76 cms, and 0.00 ± 0.44 v/s 0.62 ± 0.72 cms, p < 0.05, respectively). At the dREA, USC group were lower than USC-S group at 48 hours after EEP (−25.00 ± 9.79 v/s −43.38 ± 10.65, p < 0.05). CONCLUSIONS These results showed that the therapeutic US itself and combined with CRY may be considered as one answer for the treatment for acute muscle injuries, but more studies must be done to determine the exact US and CRY doses.