Introduction: Pain and fatigue are very common symptoms in patients diagnosed with multiple sclerosis (MS) and have the greatest effect on their activities of daily living. Aim: This study aimed to evaluate the effect of progressive muscle relaxation technique (PMRT) on pain and fatigue in patients with MS. Methods: A quasi‑experimental research with a pre‑test post‑test design was conducted on 80 patients with MS in a selected hospital in Cairo, Egypt from September 2021 to June 2022. Data were collected using the Patient Characteristics Questionnaire, Pain Effects Scale (PES) and Modified Fatigue Impact Scale (MFIS). The obtained data were analyzed in SPSS using the Paired t‑test and Pearson’s correlation analysis. Results: There was a statistically significant reduction in PES and MFIS scores from pre- to postintervention (p < 0.001), indicating a decrease in the effect of pain and fatigue on patients with MS after applying PMRT. Conclusions: These findings show that PMRT can be used as safe, convenient, inexpensive and effective method for decreasing pain and fatigue severity in patients with MS. PMRT is also recommended in the care and rehabilitation process of patients with MS.