Introduction: Physiologic alterations caused by oxidative stress can be assessed by measuring tissue malondialdehyde (MDA) levels, a biomarker for oxidative stress. The goal of this study is to determine the consequences of a twenty percent caloric restriction on the increased oxidative stress documented in tissues from rats exposed to simulated microgravity. Materials/Methods: Three groups of male SD rats (N=6 in each group) were used: Group 1, control; Group 2, food restricted (20% less food than control); and Group 3, food restricted with HLS. Group 3 was suspended after one week on the HLS-restricted diet and maintained for 14 days. Tissues harvested on day 14 were measured for MDA levels. Results: The body weight gain of Group 2 and Group 3 was reduced as compared to that of Group 1 (p <0.05) with no significant changes in water intakes. MDA levels in Group 2 were not different from those of the control group and were elevated only in liver tissues (p<0.05). In Group 3, MDA levels in the heart, liver, brain, and testes were significantly elevated (p<0.05) compared to the levels of Groups 1 and 2. Conclusions: Food restriction alleviated tissue oxidative response in all tissues except for the liver. Excessive stress resulting from HLS appeared to have been minimized by dietary restriction in all tissues except for the heart, liver, brain, and testes.