Purpose: Malnutrition is extensively prevalent amongst critically ill patients afflicted by ischemic stroke (IS). This study purpose was to evaluate the protein whey effect on inflammatory and antioxidant markers and functional prognosis in acute IS patients. Methods: out of 42 patients with acute IS who were referred to Imam Reza Educational Hospital, Tabriz, Iran, 40 patients participated in the study. Twenty-one patients as control group received the hospital routine formula, and 19 patients as intervention group received 20 g/daily of whey protein through oral gavage. Inflammation and oxidative stress indicators (e.g., albumin, malondialdehyde (MDA), total antioxidant capacity (TAC), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and high sensitivity C reactive protein (hs-CRP)and clinical variables included in were evaluated using National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) during admission and also 3 weeks after intervention. Results: Whey protein supplementation significantly decreased the NIHSS and mRS scores, TNF-α, IL-6, and hs-CRP by passing 3 weeks from intervention (P<0.05). However, whey formula had no significant effect on other markers including albumin, and MDA. The hs-CRP (P = 0.02) reduction was significantly higher in whey protein group in comparison with control group. Conclusion: Whey protein supplementation reduced inflammation markers in those patients with IS. However, these changes should be studied in larger-scale trials.