A hypervirulent strain (CB/05) of canine coronavirus was employed to infect oronasally 11-week-old pups. Peripheral blood monocytes (CD14+), T lymphocytes (CD4+ and CD8+) and B lymphocytes (CD21+) were studied by flow cytometry within 5 days post-infection (p.i.) and at later time points. Infection with CB/05 resulted in a profound depletion of T cells and a slight loss of B cells in the first week p.i. In particular, while the CD8+ and the B lymphocytes returned to baseline levels by day 7 p.i., the CD4+ T cells remained significantly low until day 30 p.i. and recovered completely only at day 60 p.i. Monocytosis was also observed after CB/05 infection with a peak at day 5 p.i. The prolonged depletion of peripheral CD4+ T cells did not alter the levels of serum IgG or IgM. The impact of CB/05 infection on the immune performance of infected pups is discussed.