Background: Environmental tobacco smoking exposure increased the level of urine cotinine and exhaled carbon monoxide (COex). Evidence suggests that there is an association between nicotine dependence and COex. The purpose of this study is to elucidate the correlation between urinary cotinine, COex, and nicotine dependence among Indonesian individuals with a history of substance use undergoing rehabilitation program. Materials and Methods: This cross-sectional study recruited participants who undergone rehabilitation at rehabilitation unit in Lido, aged >18 years old, and current smokers. We investigated the cigarette and substance consumption, Fagerstrom test for nicotine dependence (FTND), Addiction Severity Index (ASI), level of urinary cotinine, and level of COex. The ASI was determined by a psychologist who was working for rehabilitation unit. Results: The 72 assessed participants were male and aged 18-44 years old (mean 29 ± 7.1). We found significant positive correlation between urinary cotinine and COex (Spearman r = 0.3473, P = 0.0028), age of smoking initiation and age of substance use initiation (Spearman r = 0.5660, P < 0.0001), FTND and ASI (Spearman r = 0.3107, P = 0.0079), COex and age (Spearman r = 0.3323 P = 0.0043), COex and years smoking (Spearman r = 0.3028, P = 0.0097), as well as negative significant correlation COex and ASI (Spearman r = -0.2743, P = 0.0197). Conclusion: There was a significant correlation between urinary cotinine and COex, age of smoking initiation and age of substance use initiation, FTND and ASI, COex and age, COex and years smoking, and between COex and ASI. © 2018 Journal of Natural Science, Biology and Medicine | Published by Wolters Kluwer - Medknow.