In recent years, the immune suppressant corticosteroid drug prednisolone has been increasingly utilised in women undergoing IVF treatment. Prednisolone is administered in the peri-implantation phase and first trimester in the hope of improving embryo implantation rate, by lowering the risk of immunological rejections. The use of prednisolone in early pregnancy is not clinically proven except in women with specific autoimmune disorders, so the validity of its wider use is under debate. This study sought to investigate the effects of prednisolone treatment on Treg cells and pregnancy outcome in mice. CBAF1 female mice mated with Balb/c males were treated with 20 µg prednisolone or vehicle, i.p on gestational day (GD) 0.5, 1.5 and 2.5 and assessed on GD 3.5. Additional females were assessed for fetal and placental development on GD 18.5 or allowed to give birth. On GD 3.5, a decline in T helper cells (p<0.05) and a trend towards reduced Treg cell (p=0.085) was observed in prednisolone-treated compared to the control group. Amongst the Treg cells, thymus-derived Treg cell numbers showed a trend towards reduction after prednisolone treatment (p=0.063). In the blood, expression of the marker CTLA4, an indicator suppressive capacity, was lower in peripheral blood Treg cells from prednisolone treated mice (p<0.05). Prednisolone-treated mice were found to have increased pregnancy viability and increased litter size with reduced fetal and placental weight. Prednisolone-treated females deliver later than vehicle treated females, with higher rates of postnatal loss. This study demonstrates that treatment with prednisolone at a dose and time frame comparable to that utilised in women causes decreased Treg cell abundance and reduced suppressive capacity of Treg cells during early pregnancy in mice. This suggests that prednisolone may impair an essential process of the maternal immune adaptation for pregnancy, and result in poor maternal quality control on embryo implantation.