Background: Imatinib mesylate (IM) is the treatment of choice in patients with chronic myeloid leukemia (CML). Among its nonhematological adverse events, water retention is the most common, together with weight gain. However, no thorough description of the body composition in these patients has been informed. Therefore, our purpose was to evaluate the nutritional status, body composition and handgrip-strength in patients with CML treated with IM. Methods: We conducted a cross-sectional study in 78 patients (n = 48 men, 30 women) with chronic myeloid leukemia in the chronic (82%) or accelerated (18%) phases. We assessed body mass index (BMI), body composition by bioelectrical impedance, performed vector analysis through Bioelectrical Impedance Vector Analysis, and handgrip-strength measurement in patients with at least 3 months of IM treatment. Hematocrit and hemoglobin values were collected from the medical charts. Results: BMI was within the normal range in 28.2%, indicated overweight in 39.7% and obesity in 30.8%. According to BIVA, 25.6% of the patients were muscle-depleted and were older (p = 0.006) and received lower doses of IM (p < 0.001). Conclusions: In patients with CML with ≥3 months of IM treatment muscular depletion is frequent and is related to lower doses of IM.