The relationship of objective sleep parameters with health-related quality of life (HRQoL) in multiple sclerosis (MS) has not been studied.To evaluate the relationship between polysomnographic (PSG) parameters and HRQoL in MS.Ambulatory MS patients without a known sleep disorder completed the Short Form (36) Health Survey (SF-36), pain visual analog scale, and two consecutive overnight PSGs. HRQoL was assessed using SF-36 Physical and Mental Component Summary (PCS, MCS) scores. Standard objective PSG measures of sleep quality were determined. The relationship between objective sleep parameters and HRQoL was evaluated with multivariate linear regression, adjusting for age, sex, body mass index, disability, and pain.62 MS patients were included. PSG measures of sleep disruption including stage changes, awakenings, time in N1 sleep, and apnea-hypopnea and total arousal indices were negatively associated (p0.05) with MCS scores (lower scores indicating poorer HRQoL). PSG parameters reflective of better sleep quality including total sleep time, sleep efficiency, and time in REM sleep were positively associated with MCS scores. PSG parameters were not significantly associated with PCS scores.PSG-documented sleep disruption negatively impacts, while better objective sleep quality positively impacts on the mental domain of HRQoL in MS.