Multiple sclerosis (MS) is an inflammatory disease impacting the central nervous system affecting approximately 2.5 million people worldwide. Morphological changes in muscle tissue, such as muscle size and quality, may result from weakness due to decreased mobility. This study aimed to investigate asymmetries in lower limb muscle morphology via sonography in people with MS and to quantify relationships of muscle morphology measures with individual patient characteristics, muscle performance, and functional mobility. Twenty-nine Veterans with MS (52% female, 79% African-American, 48.6 ± 11.2 years old, Expanded Disability Status Scale: 3.6 ± 1.4) underwent measurement of ultrasound-measured rectus femoris (RF) muscle morphology (thickness and echo intensity), muscle performance (knee extension strength and power), and functional mobility (Timed 25-Foot Walk, 5-Times Sit-to-Stand). The more-involved limb was identified with weaker knee extension strength. Differences between more and less-involved limb were quantified using a t-test for all muscle morphology and performance outcomes. Relationships between muscle morphology, patient characteristics, performance, and functional mobility were quantified using bivariate and multivariate analysis. The more-involved limb had significantly less RF thickness (p<0.001) than the less-involved limb, but echo intensity was not different between limbs (p=0.147). The more-involved RF thickness was significantly associated with age, muscle strength, power, and gait speed, while echo intensity was associated with only muscle strength and power. Normalized RF thickness has a positive association with knee extension torque at 60 deg/sec and 180 deg/sec (p=0.003,p=0.003) and gait speed (p=0.024), whereas the corrected echo intensity values had negative associations at 60 deg/sec and 180 deg/sec (p=0.013,p=0.006). Asymmetrical differences between RF thickness measured by ultrasound are consistent with muscle strength and power asymmetries. Deficiencies in the morphology of the RF were associated with patient characteristics, knee extension muscle performance, and functional mobility. Ultrasound is an important clinical assessment tool used to identify muscle morphology asymmetries in MS. Multiple sclerosis (MS) is an inflammatory disease impacting the central nervous system affecting approximately 2.5 million people worldwide. Morphological changes in muscle tissue, such as muscle size and quality, may result from weakness due to decreased mobility. This study aimed to investigate asymmetries in lower limb muscle morphology via sonography in people with MS and to quantify relationships of muscle morphology measures with individual patient characteristics, muscle performance, and functional mobility. Twenty-nine Veterans with MS (52% female, 79% African-American, 48.6 ± 11.2 years old, Expanded Disability Status Scale: 3.6 ± 1.4) underwent measurement of ultrasound-measured rectus femoris (RF) muscle morphology (thickness and echo intensity), muscle performance (knee extension strength and power), and functional mobility (Timed 25-Foot Walk, 5-Times Sit-to-Stand). The more-involved limb was identified with weaker knee extension strength. Differences between more and less-involved limb were quantified using a t-test for all muscle morphology and performance outcomes. Relationships between muscle morphology, patient characteristics, performance, and functional mobility were quantified using bivariate and multivariate analysis. The more-involved limb had significantly less RF thickness (p<0.001) than the less-involved limb, but echo intensity was not different between limbs (p=0.147). The more-involved RF thickness was significantly associated with age, muscle strength, power, and gait speed, while echo intensity was associated with only muscle strength and power. Normalized RF thickness has a positive association with knee extension torque at 60 deg/sec and 180 deg/sec (p=0.003,p=0.003) and gait speed (p=0.024), whereas the corrected echo intensity values had negative associations at 60 deg/sec and 180 deg/sec (p=0.013,p=0.006). Asymmetrical differences between RF thickness measured by ultrasound are consistent with muscle strength and power asymmetries. Deficiencies in the morphology of the RF were associated with patient characteristics, knee extension muscle performance, and functional mobility. Ultrasound is an important clinical assessment tool used to identify muscle morphology asymmetries in MS.