Quantitative muscle ultrasound (QUS) in boys with Duchenne Muscular Dystrophy (DMD) shows increased echointensity as muscle is replaced with fat and fibrosis. Studies of quantitative ultrasound in infants/young boys with DMD over time have not been reported. Calibrated muscle backscatter (cMB), a reproducible measure of ultrasound echointensity,was used to quantify muscle pathology in 5 young boys with DMD (ages 0.5-2.8 years) over 17-29 months. Repeated assessments of function (n=4) and to muscle ultrasound images from a cross section of 6 male controls (0.6-3.1 years) were compared. cMB in boys with DMD increased (worsened) over time (P<0.001), while function improved. After age 2 years, cMB in most (4 of 5) boys with DMD was higher than in any control. QUS measures disease progression in young boys with DMD despite functional improvements. QUS could be employed as an outcome measure for serial assessment of young boys with DMD.