Horses are transported frequently and often over long distances. Transportation may represent a physiological stressor with consequential health and welfare implications. This study reports the effects of a long distance journey on immunological, clinical, haematological, inflammatory and oxidative parameters in an Experimental Group (EG) of ten horses, comparing them with six horses of similar age and breed used as a non-transported Control Group (CG). Clinical examination and blood sampling were performed twice on all horses: immediately after unloading for the EG, and at rest on the same day for the CG (day 1); at rest on the same day one week later for both groups (day 7). On day 1 EG horses showed increased heart and respiratory rates (P < 0.01), rectal temperature (P < 0.05), capillary refilling time (P < 0.01), neutrophil numbers (P < 0.01), serum albumin (P < 0.01), plasma total antioxidant status (P < 0.01), and a lower rate of mitogen induced proliferation of lymphocytes (P < 0.05), in comparison with CG. On day 7 only an increase in total serum protein (P < 0.05) and serum globulins (P < 0.001) was seen in the EG. No difference in serum cortisol concentration was found. Long distance transportation induced an acute phase response impairing the cell-mediated immune response. Clinical examinations, including assessing CRT and body weight loss, and the monitoring of redox balance may be useful in evaluating the impact of extensive transport events on horses. A better understanding of the link between transportation stress, the immune system and the acute phase response is likely to inform strategies for enhancing the welfare of transported horses.