Invasive disease is an infectious disease caused by Streptococcus pneumonia, a bacteria that caused serious infectin such as pneumonia, meningitis, and sepsis. On 2015, the health ministry estimated cases of invasive disease, especially the national pneumonia case rate was 3.55%. The purpose of this study is for knowing cost of illness of illness of invasive disease treatment in children which including direct medical cost, direct nonmadical cost, and indirect cost and also comparison between real cost and INA-CBGs cost based on Permenkes RI No 64 th 2016 in pediatric patients of invasive disease patient hospitalized at RSUD Yogyakarta. The design of this research was conducted by analytic observational approach with cross sectional design based on societal perspective that held on September 2017 – February 2018. Sampling method was obtained by questioner in interview of patient’s parents/trustees and also extracting medical record and medical cost pediatric patients of invasive disease in patient at RSUD Yogyakarta. Methods of data analysis used descriptive statistics that included direct medical cost data, direct nonmedical cost, and indirect cost of 38 pneumonia and 3 sepsis patients. Comparison between real cost and INA-CBGs cost was done by using independent t-test method. The result of cost analysis during the period of ≤6 months were 18 patients of pneumonia based on INA-CBGs J-4-16-1 code of 16 patients, INA-CBGs J-4-16-1 code of 2 patients, and 3 sepsis patients based on code INA-CBGs A-4-10-1. Total cost of illness of pediatric patients of invasive disease is 124.330.877 IDR for 41 in patients with 5.927.077 IDR in average with the largest component on direct medical cost for medicines and medical devices. Based on long term of hospitalization, treatment classes showed significant differences (p> 0.05) with the greater INA-CBGs cost than has no significant difference (p > 0.05) with the greater INA-CBGs cost than real cost of sepsis patients. This showed that RSUD Kota Yogyakarta managed the INA-CBGs cost well and did not incur disadvantages to the hospital for pediatric patients of invasive disease.