Background: FSHD is a neuromuscular disease affecting different muscles across the body and impacting distinct regions within the same muscle. It is unclear how muscle morphology (assessed via ultrasound), specifically muscle thickness (MT) and muscle quality (MQ), varies across the muscle’s length in FSHD. Additionally, the effects of a single bout of resistance exercise on muscle function and morphology in FSHD are unknown. Purpose: 1) Evaluate MT and MQ (via echo intensity) across the length of affected muscles, and 2) evaluate acute responses to an exercise-challenge test in individuals with FSHD. Methods: FSHD patients (n=7, 43% women; 46.4±16.0 years) with clinical diagnosis were recruited and had their physical function (TUG test; SPPB; stair climb and upper and lower limb maximal voluntary isometric torque – MVIT) evaluated. Moreover, ultrasound measurements, across the length of the muscle, from the biceps brachii (BB), vastus lateralis (VL), rectus femoris (RF), and vastus intermedius (VI) were performed. Results: MT was greater at 30% vs. 70% of the muscle’s length for VL, RF, and VI (P<0.05). MQ was also greater at 30% vs. 70% of the muscle’s length for VL and RF (P<0.05). BB MT and MQ were greater at 50% vs. 70% of the muscle’s length. Elbow flexion MVIT decreased from pre- vs. post-exercise (P<0.05), while knee extension MVIT was unchanged. Both MT and MQ were changed in the BB from pre- vs. post-exercise (P<0.05). MT increased across the length of the VL and RF after the exercise (P<0.05), while MQ only changed in the VL from pre- vs. post-exercise (P<0.05). Conclusion: Different muscles show distinct changes in muscle size and quality at baseline and in response to acute exercise in FSHD patients. Our findings agree with previous data from MRI showing changes from proximal to distal across the length of the lower limb muscles.