Background: Breast milk is rich in microRNAs that is important for human growth, development, and immune–mediated protection. The method of delivery could alter the wide range of compounds and bioactive molecules present in the human breast milk. Objectives: in this work we studied the expression of the immune-related miRNAs (miR-181a, miR-150, and miR-146) in colostrum and mature human milk in normally delivered and cesarean section delivered females to assess the delivery method impact on their expression levels. Methodology: a cross-section study included 32 females; 16 delivered by normal vaginal delivery and 16 by cesarean section. Colostrum and mature milk were obtained from each female and the expression level of miR-181a, miR-150, and miR-146 were assessed. Results: The expression of miR-181a and miR-146 were significantly higher in colostrum than mature breast milk among all participants (P 0.008, 0.020) and among normal vaginal delivery women (P 0.019, 0.045). While only miR-181a was significantly expressed in colostrum than mature breast milk of cesarean section delivered women (P 0.012). Conclusion: The immune-related miRNAs (miR-181a, miR-146 and miR-150) are variably expressed in colostrum and mature milk of mothers gave birth by different methods of delivery. Thus, feeding newborns with all breast milk stages is essential to help their immune system development and maturation and the mode of delivery affects the bioactive molecules profiles in human breast milk.