Cachexia is a multifactorial syndrome characterized by progressive weight loss, muscle wasting, metabolic disturbances, and chronic inflammation, and is frequently associated with parasitic, infectious, and neoplastic diseases in sheep. This study aimed to investigate haematological, biochemical, and anatomopathological alterations associated with cachexia using an integrated multisystemic approach. A cross-sectional observational study was conducted on 139 sheep examined at the slaughterhouse of Tiaret province, Algeria. Animals were classified by body condition score into cachectic (n = 90) and non-cachectic control groups (n = 49). All animals were subjected to routine ante-mortem and post-mortem veterinary inspection by official inspectors in accordance with slaughterhouse regulations. Samples were collected during routine slaughterhouse procedures without interfering with veterinary inspection. Haematological and biochemical analyses were performed using automated analysers, while gross and histopathological examinations were conducted on affected organs. Cachectic animals showed significant leucocytosis, neutrophilia, monocytosis, eosinophilia, lymphopenia, and normocytic normochromic anaemia, with decreased erythrocyte count, haemoglobin concentration, and haematocrit (p < 0.05). Biochemical alterations included increased AST, ALT, and urea, together with hypoalbuminaemia, hypoproteinaemia, and a reduced albumin/globulin ratio. Correlation analysis revealed strong associations among erythrogram variables, protein profile indices, and inflammatory leukocyte populations, indicating coordinated metabolic and inflammatory dysregulation. Pathological examination revealed multisystemic lesions mainly affecting the gastrointestinal tract, lungs, liver, and abomasum, characterized by parasitic, granulomatous, chronic inflammatory, suppurative, and neoplastic lesions. These findings indicate that cachexia is a complex systemic syndrome resulting from interacting parasitic, infectious, inflammatory, and neoplastic processes. The integration of haematological, biochemical, and pathological data provides insight into its systemic nature and supports improved surveillance, early detection, herd health management, and animal welfare in small ruminants.