Objective: Protein-energy malnutrition (PEM) is an important public health problem affecting millions of people worldwide. Hematopoietic tissue requires a high nutrient supply, and a reduction in leukocytes, especially lymphocytes, suggests that some nutritional deficiencies might be altering bone marrow function and decreasing its ability to produce lymphocytes. In this study, we evaluated the effect that PEM has on lymphocyte subtypes and the cell cycle of CD5+ cells. Methods: Swiss mice were subjected to PEM using a low-protein diet containing 4% protein. When the experimental group had lost about 20% of their original body weight, we collected blood and bone marrow cells and evaluated the hemogram, the myelogram, bone marrow lymphoid markers using flow cytometry, and the cell cycle in CD5+ bone marrow. Results: Malnourished animals presented anemia, reticulocytopenia, and leukopenia with lymphopenia. The bone marrow was hypocellular, and flow cytometric analyses of bone marrow cells showed cells that were CD45+ (91.2%), CD2+ (84.9%), CD5+ (37.3%), CD3+ (23.5%), CD19+ (43.3%), CD22+ (34.7%), CD19+/CD2+ (51.2%), CD19+/CD3+ (24.0%), CD19+/CD5+ (13.2%), CD22+/CD2+ (40.1%), CD22+/CD3+ (30.3%), and CD22+/CD5+ (1.1%) in malnourished animals and CD45+ (97.5%), CD2+ (42.9%), CD5+ (91.5%), CD3+ (92.0%), CD19+ (52.0%), CD22+ (75.6%), CD19+/CD2+ (62.0%), CD19+/CD3+ (55.4%), CD19+/CD5+ (6.7%), CD22+/CD2+ (70.3%), CD22+/CD3+ (55.9%), and CD22+/CD5+ (8.4%) in control animals. Malnourished animals also presented more CD5+ cells in the G0 phase of cell cycle development. Conclusion: Malnourished animals presented bone marrow hypoplasia, maturation interruption, prominent lymphopenia with depletion in the lymphoid lineage, and changes in cellular development. We suggest that these changes are some of the primary causes of lymphopenia in cases of PEM and partly explain the increase in susceptibility to infections found in malnourished individuals.