Introduction: Anorexia is a major symptom of cachexia for a large number of cancer patients, disrupting the physiological regulation of food intake and contributing to the deterioration of health status. Data from literature suggest that mechanisms underlying cancer-associated anorexia may involve both central and peripheral mediators, such as IL-6 and GDF15 cytokines, but they are poorly understood. Our objective was to study the mechanisms associated to the transition from pre-anorexia to anorexia. Methods: We chose the C26 tumor-bearing mouse model characterized by a decreased food intake and loss of body weight (Bindels et al., Oncotarget 2018). The food intake of C26- and Sham male mice was measured daily. We performed biological analyses on two groups of C26-mice, on pre-anorexia stage and early stage of anorexia. Results: The onset of anorexia was associated with a significant increase in the weight of tumor, spleen and liver. In the hypothalamus, a key site of food intake regulation, the mRNA expression level of IL-6, IL-1β and TNF cytokines were not affected. The expression level of the orexigenic neuropeptide NPY was significantly increased. At the peripheral level, food intake was inversely correlated with plasma levels of IL-6 and GDF15 cytokines (R2=0.82 and 0.70, respectively). Plasma GDF15 concentrations correlated with tumor mass (R2=0.57), but the expression level of GDF15 mRNA did not change over time in the tumor, whereas it was increased in liver and intestine. Conversely, the expression level of IL-6 mRNA was high and increased over time within the tumor whereas it was not detectable in liver and intestine. Conclusions: The magnitude of anorexia is correlated with circulating levels of IL-6 and GDF15, underlying the potential involvement of these cytokines. However, IL-6 and GDF15 expressions are regulated in different ways among the different tissues.