This study investigates the pivotal role of chicken interferon-gamma (ChIFNgamma) in the pathogenesis and immunosuppression of infectious bursal disease virus (IBDV) infection and is divided into in vivo, ex vivo and in vitro experiments. Two-week-old specific pathogen free chickens were inoculated with the 849VB very virulent strain of IBDV. The levels of systemic ChIFNgamma and chicken interleukin-6 in the serum were followed for 2 weeks during in vivo experiments. Then, splenocytes and bursal cells from infected chickens were analysed for their immunocompetence after mitogenic activation in ex vivo experiments. Finally, in vitro experiments were conducted to assess the direct immunosuppressive effect of ChIFNgamma on splenocytes and peripheral blood lymphocytes from non-inoculated specific pathogen free chickens. Our results reveal that the acute phase of infectious bursal disease coincides, on one hand, with high levels of systemic ChIFNgamma and chicken interleukin-6 and, on the other hand, with a strong inhibition of proliferation and activation of mitogen-stimulated splenocytes from infected chickens, as measured by ChIFNgamma production. Two weeks after viral inoculation, T lymphocytes infiltrating the bursa of Fabricius had recovered their activation capability. Finally, an in vitro study showed that the proliferation of naïve splenocytes and peripheral blood lymphocytes was directly and specifically inhibited by ChIFNgamma. In conclusion, a ChIFNgamma dysregulation occurs in chickens infected with IBDV and the overproduction of ChIFNgamma by T lymphocytes plays a key role in the pathogenesis and immunosuppression induced by this virus.