Background: Mother-infant skin to skin care (SSC) has gaining increasing interest as an effective method for infant care. Electroencephalogram (EEG) is effective inexpensive tools for evaluation of maturational brain changes through assesses resting EEG wave powers. Objectives: To evaluate the relationship between maternal SSC and changes in brain activity detected by electroencephalographic brain mapping. Methodology: This study is a non-randomized QUASI experimental study using a pre and posttest on the infants in the form of maternal-infant SSC for 30 minutes without a control groups. The study was carried out on 100 apparently healthy infants aged 4 to 6 months of both sex and exclusive breastfeeding. All infants underwent full history taking, thorough clinical examination of all body systems, and electroencephalographic brain mapping analysis before and 30 minutes after maternal-infant SSC. Results: There was a statistically significant increase in mean power of alpha and theta frequency bands after 30 min of SSC in comparison to before SSC. There was a statistically significant increase in mean power of both alpha and theta frequency bands in females infants in comparison to males. There was a statistically significant decrease in heart rate and respiratory rate in the studied infants after 30 min SSC in comparison to before SSC. Conclusion: maternal-infant SSC is associated with global improvement of brain activity regardless of the area of the brain. The brain of female infants has a better response to the SSC than male.