Abstract Relationships between birth weight and a range of immune markers were studied in piglets during the peri-weaning period. A total of 47 sows and their respective litters adjusted to 12 piglets were used. Piglets were weighed after birth and within each litter 2 low weight (LW) and 2 high weight (HW) animals were identified: the average weight of the 2 groups was 1.12 and 1.81 ± 0.17 kg, respectively. Within litter, one couple of LW and HW piglets was sacrificed at 16 and 23 d of age, two days after weaning at day 21, to characterise different leukocyte subsets in mesenteric lymph nodes (MLN) and blood by flow cytometry. Jejunal mucosal and MLN samples were also collected to measure the expression of genes involved in immune response by qPCR. The percentage of blood γδT cells was higher in HW piglets before and after weaning (P=0.01 and P<0.001, respectively). At 16 d, LW animals had higher amounts of CD4+CD8+ T cells and dendritic cells in the blood (P=0.01 and P=0.04, respectively) and in MLN (P=0.02 and P=0.009 respectively), and lower count of blood cytotoxic T cells (P=0.01) than HW. Moreover, jejunal expression of TNFα was reduced in LW piglets (P=0.02), while MLN expression of CCL23, BMP2 and SPP1 was increased (P=0.003, P=0.002 and P=0.02, respectively). Two days after weaning (d 23), HW piglets had higher percentages of T cells (P=0.001) and lower amount of non-T cells (P=0.03) and natural killer cells (P=0.04) in blood compared to LW animals. These data revealed that piglet birth weight affects the proportion of leukocyte subsets in different tissues and the expression of genes involved in the immunity. Globally, our results suggest that the development of the immune system after birth differed between LW and HW piglets.