Weaning is a necessary husbandry practice in which nutritional, social, physical and psychological stressors are imposed on the beef calf causing alterations in behavioural and physiological responses. To date, few studies have examined the effect of weaning on the extended physiological and immunological responses of beef calves and cows. Furthermore, no research has examined the effect of weaning stress on leukocyte immunophenotypes expressing selected differentiation antigens and the functional activity of neutrophils in calves. A series of studies were conducted to investigate i) the effect of weaning strategy (at pasture or housing) on the extended physiological and immunological responses of calves, ii) the effect of weaning and subsequent housing on physiological and immunological responses of cows and iii) the effect of weaning on leukocyte immunophenotypes and neutrophil activity of calves. Results indicate that weaning in combination with immediate housing decreased total leukocyte numbers, reduced in vitro production of interferon-gamma and increased concentrations of acute phase proteins compared with deferring housing for 35 days post weaning. In cows, transitory neutrophilia (increase in neutrophil number) and lymphopenia (decrease in lymphocyte number), reduced interferon-γ production, and increased concentrations of acute phase proteins were evident post weaning, whereas post-housing, changes were less marked. Weaning caused neutrophilia and impaired the functionality of these cells to traffic and efficiently phagocytise bacteria up to 7 days post weaning. Altered lymphocyte subsets and MHC Class II+ cell percentage were evident in weaned and non-weaned calves on day 2 post-weaning, however the magnitude of change was greater in weaned calves. Thus, there is a greater transitory reduction in immune function biomarkers in calves immediately post weaning. These immune biomarkers may be used in the future to help identify animals susceptible to weaning stress and that are more likely to succumb to respiratory infection.