Purpose To evaluate whether sunitinib and pazopanib treatments are associated with change in skeletal muscle area (SMA) and total lean body mass (LBM) as well as to compare their efficacies and safety profiles in patients with metastatic renal cell cancer (mRCC). Methods Thirty-six patients treated with a tyrosine kinase inhibitor were included. Eighteen of them received sunitinib and the rest/remaining received pazopanib in the first line of mRCC treatment. Baseline and follow-up computed tomography studies of the patients were performed to measure cross-sectional areas (cm 2 ) of muscle tissues. Results About 69% of patients were male and median age was 60 (49–68) years. Median time interval between two CT imagings was 6.1 (3.1–7.7) months and it was similar between the two groups (for sunitinib, 4.9 (2.5–6.9) months vs for pazopanib, 7.3 (3.2–9.5) months, p  = 0.16, respectively). Disease control rate was 77.7% in all patients. Of these, 66.6% in sunitinib group was consisted of four partial responses and eight stable diseases. In addition, 88.8% in pazopanib group was consisted of three partial responses and 13 stable diseases. A significant decrease in SMA and LBM was observed after sunitinib therapy, whereas SMA and LBM values of pazopanib group did not change significantly ( p  = 0.02 and p  = 0.70, respectively). No significant differences were observed between patients with sunitinib, and pazopanib group median PFS 11.9 (95% CI 6.1–17.6) vs 8.1 months (95% CI 7.2–9.1), respectively; p  = 0.28 and median OS 28.6 (95% CI 24.3–32.9) vs 25.5 months (95% CI 18.9–52.7), respectively; p  = 0.42. Dose-limiting toxicities were significantly more frequent in sunitinib group than in pazopanib group (66.7% vs 22.2%, p  = 0.02, respectively). Conclusions Loss of SMA and LBM with sunitinib was more substantial than with pazopanib. Treatment efficacies of both drugs were similar, but dose-limiting toxicity was more frequent in sunitinib group. Loss of SMA had no significant association with prognosis. Further studies are needed to clarify the possible association between SMA and prognosis in mRCC patients who receive sunitinib or pazopanib.