Self-medication with antibiotics is becoming a very common practice, and it is being practiced globally carrying a significant economic burden and health hazards. This study assesses prevalence and predictors of self-medication with antibiotic for children. A cross-sectional study was carried out on 252 mothers selected randomly from primary health care Centers in Makkah, during the period Jan -July 2016. Mothers were interviewed about giving their children antibiotic without prescription using a semi structured questionnaire. Data was analyzed using IBM advanced SPSS statistical package version 23. Logistic regression analysis was done to determine which of the factors are independently associated with self-medication with antibiotic for children. As a result, in total, 252 respondent mothers were interviewed with mean age 36.7±18.4. The prevalence of self-medication with antibiotic for children was 39.3% despite that the majority 82.9% has satisfactory knowledge about proper antibiotic use. Amoxicillin clavulenic is the most self-prescribed antibiotic representing 53.3% followed by amoxicillin 25.6%. The predictors for self-medication were educational level, income, residence and knowledge about antibiotics use. It was concluded that, Self-medication with antibiotics for children is a common practice. Policies and considerable efforts are needed to challenge the self-medication with antibiotics especially increasing the awareness among mothers about the self-medication with antibiotics risks and hazards.