Background: Iran is a significant consumer of opium, and, generally, of opioids, in the world. Addiction is one of the important issues of the 21st century and is an imperative issue in Iran. Long-term consumption of opioids affects homeostasis. Objective: To determine the effects of opium and heroin consumption on serum biochemical parameters. Methods: In a cross-sectional study, subjects who had consumed heroin (n = 35) or opium (n = 42) for more than two years and 35 nonaddict volunteers as the control group were compared in regard to various biochemical parameters such as fasting blood sugar (FBS), Na⁺, K⁺, Ca²⁺, blood urea nitrogen (BUN), uric acid (UA), triglyceride (TG), cholesterol, creatinine, and total protein. Chromatography was used to confirm opioid consumption, and the concentration of biochemical parameters was determined by laboratory diagnostic tests on serum. Results: No significant differences were found in Na⁺, Ca²⁺, BUN, UA, TG, creatinine, and total protein concentrations among the three groups. FBS, K⁺, and UA levels were significantly lower in opium addicts compared to the control group. Serum Ca²⁺ concentration of heroin addicts showed a significant decrease compared to that of the control group. Both addict groups showed a significant decrease in serum cholesterol levels. Conclusion: Chronic use of opium and heroin can change serum FBS, K⁺, Ca²⁺, UA, and cholesterol. Scientific Significance: This study, one of few on the effects of opium on serum biochemical parameters in human subjects, has the potential to contribute to the investigation of new approaches for further basic studies.