Trypanosoma brucei brucei causes animal trypanosomiasis in several vertebrates and human African trypanosomiasis. Previous studies have only explored the incidence, clinical symptoms, haematology and biochemical changes associated with the disease. The behavioral manipulation hypothesis posits that parasites alter the behavior of host to increase the reproductive abilities of such parasites. Hence, the present study was carried out to investigate changes in behavior and cognition following experimental infection of T. brucei brucei in rat model. This study involved two groups of animals (uninfected control and T. brucei infected) with 8 rats per group. After confirmation of parasitaemia in the infected rats both groups were assessed to investigate if infection led to behavioral alterations and neuropathological changes using the open field, social interaction and forelimb suspension tests. Immunohistochemistry was performed on brain tissues using glial fibrillary acidic protein and anticalbindin-D28k, antibodies. We demonstrated that T. brucei infection triggered a significant decrease in exploratory activity, anxiety-like behavior, altered recognition of social novelty and reduced hanging latency in the hanging wire test. Immunohistochemistry revealed significant astrocytosis, loss of dendritic spines and reduction of Purkinje cell layer of the cerebellum. These results demonstrate that T. brucei infection induce signs of anxiety, impaired motor co-ordination with degeneration and loss of Purkinje cells.