The high use of antibiotics in the community will lead to resistance. According to the results of studies in Indonesia, the problem of antibiotic resistance is very complex and will continue to increase every year. Infectious diseases account for more than 13 million deaths per year in developing countries. Wise and rational use of antibiotics can reduce the disease burden, especially infectious diseases. Conversely, the widespread use of antibiotics that do not match the indications significantly increases antibiotic resistance. Students must know the proper use of antibiotics so as not to develop antibiotic resistance. They do not know much or fully understand antibiotics during the transition from childhood to adulthood. This study aims to determine the relationship between knowledge, attitudes, and behavior of SMAN Se-Kota Pekanbaru students in the use of antibiotics. This research uses a descriptive survey method with 360 respondents. Data analysis was done using a chi-square test with a significance level of p 0.05. The results of this study showed that there were students with good knowledge (67%), with some who showed a positive attitude (75%), and less behavior in the use of antibiotics (74%). The chi-square test showed a significant relationship between attitudes and antibiotic use behavior with a p-value of 0.001 (p 0.005). While the level of knowledge and attitude had a p-value of 0.605 (p 0.05) and the level of knowledge and behavior had a p-value of 0.118 (p 0.05), indicating there was no significant relationship. From the results of this study, it can be concluded that there is no significant relationship between students' knowledge with attitudes and behavior in the use of antibiotics, and there is a significant relationship between attitudes and student behavior in the use of antibiotics.