Feed strategies such as compensatory growth and protein restriction have been applied to optimize growth and feed efficiency in aquatic species. The effects of protein restriction (from 1 to 4 weeks of feeding with dietary 35% protein) and 1 week of fasting on growth, body composition, hemolymph parameters, digestive enzymes, serological enzymes, immune and antioxidant system, and relative gene expressions in whiteleg shrimp (Litopenaeus vannamei) (0.30 ± 0.03 g) were investigated. Treatments were experienced in 1 out of 8 weeks of fasting but not in the Control and 35%P groups. Other groups were 7P40 (1-week fasting), 6P40 (1-week feeding dietary 35% protein), 5P40 (2-week feeding with dietary 35% protein), 4P40 (3-week feeding dietary 35% protein), and 3P40 (4-week feeding dietary 35% protein). The results indicated that there was no difference in weight gain among Control (10.22 g), 7P40 (9.37 g), and 6P40 (9.27 g) groups. Feed efficiency in 35%P was significantly lower than in Control. The 5P40, 4P40, 3P40, and 35%P treatments had lower protein and lipid contents in the body, protease, total protein, and cholesterol compared with the Control. Immunity and antioxidant systems were suppressed by the application of fasting and protein restriction simultaneously so that acid phosphatase, lysozyme, superoxide dismutase, glutathione peroxidase, and lysozyme gene in 4P40, 3P40, and 35%P treatments were lower, and also, these groups had higher alanine aminotransferase levels than the Control. In conclusion, this study suggests that applying both protein restriction and fasting impairs the growth and health of whiteleg shrimp, and at least 6 out of 8 weeks, whiteleg shrimp should be fed with a dietary 40% protein.