(cachexia) is severe in patients with colorectal liver metastases because of the large increase in resting energy expenditure but remains understudied because of a lack of suitable preclinical models. Our aim was to characterize a novel preclinical model of cachexia in colorectal liver metastases. We tested the hypothesis that mice with colorectal liver metastases would exhibit cachexia, as evidenced by a reduction in liver-free body mass, muscle mass, and physiological impairment. Twelve-week-old male CBA mice received an intrasplenic injection of Ringer solution (sham) or murine colorectal cancer cells (MoCR) to induce colorectal liver metastases. At end-point (20 -29 days), the livers of MoCR mice were infiltrated completely with metastases, and MoCR mice had reduced liver-free body mass, muscle mass, and epididymal fat mass compared with sham controls (P Ͻ 0.03). MoCR mice exhibited impaired rotarod performance and grip strength (P Ͻ 0.03). Histochemical analyses of tibialis anterior muscles from MoCR mice revealed muscle fiber atrophy and reduced oxidative enzyme activity (P Ͻ 0.001). Adipose tissue remodeling was evident in MoCR mice, with reduced adipocyte diameter and greater infiltration of nonadipocyte tissue (P Ͻ 0.05). These findings reveal the MoCR mouse model exhibits significant cachexia and is a suitable preclinical model of cachexia in colorectal liver metastases. This model should be used for identifying effective treatments for cachexia to improve quality of life and reduce mortality in patients with colorectal liver metastases. muscle wasting; cancer cachexia; muscle weakness; colorectal liver metastases CANCER CACHEXIA IS DEFINED as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support, leading to progressive functional impairment (8). Cachexia occurs in up to 80% of patients with advanced cancers of the gastrointestinal tract, colon, lung, breast, sarcoma, and prostate (33). It is also present early in the progression of gastrointestinal, pancreatic, and lung cancers (33). Cachexia reduces mobility and functional independence and causes severe fatigue, which together reduce overall quality of life (26). Cachexia can also increase the risk of postoperative complications, impair the response to antineoplastic treatments, and result in the eventual failure of respiratory and cardiac muscle function that causes 20 -30% of all cancer-related deaths (33). Unfortunately, there is no Food and Drug Administration-approved treatment for cancer cachexia, and this is due, at least in part, to a lack of suitable preclinical models that closely mimic the human condition for maximizing translational outcomes (24).Colorectal cancer is the third most common cancer worldwide and is the fourth-most common cause of cancer-related death (9). The most frequent complication of colorectal cancer is the development of liver metastases, which occurs in 70% of cases and is the main cause ...