Objectives The present study investigated the effectiveness of Acceptance and Commitment Therapy (ACT) on Chronic Fatigue Syndrome (CFS) and Pain Perception (PP) in people with Multiple Sclerosis (MS). 
Methods This was a quasi-experimental study with a pre-test, post-test and a control group design. The statistical population was all individuals with MS referring to the MS Society of Ahvaz, Iran, in 2018. Thirty patients with SFS were selected and randomly assigned into two groups of test and control (15 per group). Moreover, Multidimensional Fatigue Inventory (MFI) (was used to measure chronic fatigue symptoms) and Fatigue Severity Scale (FSS) and McGill Pain Questionnaire (MGPQ) were used for data collection. The achieved data were analyzed by Multivariate Analysis of Covariance (MANCOVA) in SPSS. 
Results The MANCOVA results revealed a significant difference between two groups in the following variables: perception of sensory pain (F=14. 70, P≤ 0. 001), perception of pain assessment (F=70. 50, P≤0. 01), perception of various pain (F=8. 13, P≤0. 001), PP (F=14. 68, P≤0. 001,) and CFS (F=4, P≤0. 05). 
Conclusion The study finding suggested that ACT was effective in reducing the severity of CFS and PP in the experimental group; this reduction has led to a relative improvement in MS condition. Therefore, clinicians working in health centers can use this treatment along with pharmacotherapy.