Interleukin-15 (IL-15) has important anabolic effects on muscle protein metabolism through a decrease in the ATP-ubiquitin-dependent proteolytic pathway. The role of IL-15 in human cancer cachexia is unknown. The aim of this study was to assess the relationship between interleukin-15 (IL-15) in cancer patients with cachexia at diagnosis of malignancy and 8 weeks later. An observational study of 21 cancer patients (with and without cachexia) and 8 healthy subjects was conducted. Body composition was measured by leg-to-leg impedance. Serum IL-15 levels were assessed at baseline and after 4 and 8 weeks. Baseline IL-15 values were similar in cancer patients and in healthy subjects. Cancer patients with lower baseline levels of IL-15 (<2 pg/ml) had significantly higher fat mass (%) along the study. Eighteen patients completed the study: five patients showed an increase of 3.7 kg at the end of the study (5.4% of body weight) and showed a mean increase of IL-15 of 1.32 pg/ml (121%) at 4 weeks and 2.32 pg/ml (197%) at 8 weeks, as compared with mean decrease of -4.1 kg (-5.3%) and -0.09 pg/ml (-2.5%) and 0.6 pg/ml (40.8%) in the 13 patients who lost weight (P=0.001 and P=0.022, respectively). Changes of IL-15 at 4 and 8 weeks were directly associated with changes in body weight, body mass index (BMI), fat-free mass and muscle mass (P<0.05), and indirectly associated with percentage of weight loss (P<0.05). In summary, although the results indicate that IL-15 does not have a role in cancer cachexia pathogenesis, the association during evolution between serum IL-15 and changes in weight and muscle mass suggests a possible role of IL-15 as a marker of the body composition response in cancer patients who are losing weight at the time of diagnosis.