Although the physiology of minipuberty are well-established, it is not fully explained why it occurs. It has been suggested that minipuberty contributes to the development of reproductive organs, somatic growth, cognitive/behavioral, and sex-specific brain development. Given the well-known trade-off between the reproductive/endocrine and immune systems in adults, the immunological approach to minipuberty, which is characterized by transient activation of the hypothalamo-pituitary gonadal (HPG) axis seems to be ignored. This study focused on the relationship of the lymphocyte subsets with gonadotrophin and sex hormones during the minipuberty.A total of 121 newborns (58 male) were included in this cross-sectional study. The hormone and lymphocyte subsets studied were as follow:follicle-stimulating hormone (FSH), luteinizing hormone (LH) estradiol (E), testosterone (T), CD19, CD16/56, CD3, CD3/CD4, CD3/CD8, and HLA-DR as lymphocyte activation marker.The mean FSH levels were higher in females (15.15±10.12mIU/mL vs, 2.61±1.74mIU/mL) and LH in males (5.80±2.51mIU/mL vs. 1.91±12.89mIU/mL) (p<0.001 for each). The mean percentages of the CD3/CD4 levels were higher in females (54.61±6.70% vs. 51.17±6.77%) and CD3/CD8 in males (21.49±4.82% vs. 17.31±3.66%) (p <0.001 for each). In the females, the mean FSH levels negatively correlated with CD3/CD4 (rFSH-CD3/CD4 =-0.423, p=0.001) and positively correlated with CD3/CD8 (rFSH-CD3/CD8 =0.311, p=0.013). In the males, LH positively correlated with CD3/CD4 (rLH-CD3/CD4 =0.406, p<0.001) and negatively correlated with CD3/CD8 (rLH-CD3/CD8 =-0.486, p<0.001).This study showed that the mean CD3/CD4 levels were higher in female and CD3/CD8 in male newborns, indicating that there was a sexual dimorphism in favor of immunostimulant in females and immunosuppressor components of immune response in males during the minipuberty. These interactions point to sex-specific trade-off between reproductive/endocrine and immune systems, which it reflects the an investment favoring in the reproductive system against the immune response during minipuberty, which is critical period for adult fertility, especially in males.