Objective: There is evidence that motor and cognitive impairments often co-occur in multiple sclerosis (MS). There is little research on influences of cognitive-motor coupling, particularly depressive symptoms. This study examined depressive symptoms as a moderator and/or confounder of cognitive-motor coupling in persons with MS. Method: The sample included 131 persons with MS who were allocated into elevated and nonelevated depressive symptom groups based on a cutoff score of 8 on the Hospital Anxiety Depression Scale. We assessed lower (i.e., 6-Minute Walk Test, Timed 25-Foot Walk Test) and upper (i.e., Nine-Hole Peg Test) body function as well as cognition (i.e., the Symbol Digit Modalities Test, CA Verbal Learning Test, and Brief Visuospatial Memory Test) in a research laboratory. Depressive symptomology was investigated as a moderator and/or confounder of cognitive-motor coupling using correlation and linear regression analyses. Results: Upper and lower body function, but not cognition, differed significantly between depressive symptoms groups (p < .05). Scores on the motor and cognitive tests were uniformly correlated between depressive symptom groups. Depressive symptom category did not confound the coupling between motor and cognitive functions, and explained additional, but minimal, variation in the lower body motor function scores (p < .05). Conclusion: Strong coupling between motor function and cognitive processing speed in MS appeared to be consistent between depressive symptom groups. Elevated depressive symptoms might influence motor functioning more strongly than cognitive functioning in MS.