Foot-related diseases are among the most common herd health issues worldwide, leading to heavy burden on the sheep and their owner including heavy socio-economic losses. This study investigated the haematological, serum biochemical and acute phase protein profiles of sheep with footrot infection caused by Dichelobacter nodosus. Blood samples from 15 sheep with footrot and 10 healthy controls were collected and analyzed for possible alterations in haematological, serum biochemical parameters and acute phase protein (APPs). Sheep with footrot showed significant changes in haematological parameters including left-shift, neutrophilic leukocytosis, lymphopenia and monocytosis. Serum biochemical assay revealed significant (P<0.05) increase in the concentration of total protein, cortisol, glucose, haptoglobin and fibrinogen while the concentration of albumin was significantly decreased. The finding of this study emphasizes the importance of haematological, serum biochemical and APP analytes in the diagnosis and monitoring of footrot in sheep. The finding of this current study could be used for the development of point-of-care diagnostic markers that would aid prompt diagnosis and treatment of footrot in sheep.