Background: Pain and fatigue are highly prevalent in multiple sclerosis (MS) and are associated with adverse outcomes spanning the physical, social, and psychological domains. There is thus a critical need to identify modifiable factors that can reduce the impact of these symptoms on daily life. Objectives: This study examined: 1) associations between coping strategy use and daily functional and affective outcomes; 2) the moderating role of coping strategy use in the relationship between daily fluctuations in pain and fatigue and same-day outcomes. Methods: Ambulatory adults with MS (N=102) completed a baseline self-report measure of coping strategy use followed by 7 days of home monitoring during which they completed ecological momentary assessments of pain and fatigue (5x/day) and end-of-day diaries assessing same-day pain interference, fatigue impact, social participation, upper extremity (UE) and lower extremity (LE) functioning, depressive symptoms, and positive affect and well-being (PAWB). Multilevel mixed models tested associations between use of avoidant/approach coping and daily functional/affective outcomes and interactions between daily changes in symptoms and coping strategy use in predicting same-day outcomes. Results: More frequent use of avoidant coping was associated with worse pain interference (B=.38, p<.001), fatigue impact (B=.18, p=.002), social participation (B=-.27, p=.001), LE functioning (B=-.28, p=.02), depressive symptoms (B=.36, p=.002), and PAWB (B=-.44, p=.004). More frequent use of approach coping was associated with higher PAWB (B=.20, p<.05). There were significant interactions between daily pain and avoidant and approach coping in predicting same-day pain interference; daily pain and approach coping in predicting same-day PAWB; and daily fatigue and avoidant coping in predicting same-day PAWB. Probing these interactions revealed avoidant coping to be related to worse outcomes and approach coping to be related to better outcomes. Conclusions: These findings indicate an important role of coping in determining pain- and fatigue-related outcomes in the daily lives of people with MS. When confronted with pain and fatigue, avoidant coping is associated with higher risk for functional and affective difficulties, whereas approach coping is associated with lower risk. Decreasing use of avoidant coping and increasing use of approach coping may help individuals with MS mitigate the negative impact of symptom exacerbations in daily life.