Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. It is considered the fourth leading cause of death worldwide. It is associated with a large number of comorbidities. Objective: to evaluate the important role of the biochemical investigations and shed light on smoking as environmental factor on COPD patients and passive smokers. Patients and Methods: The study conducted on 27 healthy controls, 40 passive smokers and 40 COPD patients selected by using easy sampling method in Ain Shams University Hospitals. All individuals were subjected to: thorough history taking, clinical examination, Pulmonary function tests(FEV1&FEV1/FVC), arterial blood gases analysis (ABG) and biochemical blood analysis such asCBC, ESR, alpha one antitrypsin (A1AT), C-reactive protein (CRP), serum & sputum nitric oxide (NO),fibrinogen, other liver function tests (ALT, AST&ALB)and kidneyfunction tests (BUN & Creatinine) Results: FEV1&FEV1/FVC significantly lowerin COPD patients than in passive smokers and controls. ABG analysis (Pco2) significantly higher but Po2 significantly lowers in COPD patients than in passive smokers and controls. Biochemical blood analysis for serum A1AT, NO, ALB, Hb & PLT significantly lower in COPD patients than in passive smokers and controls. Levels of plasma fibrinogen, CRP, sputum NO, (ALT & AST), (BUN & Creatinine) and (ESR, WBC & NE%) significantly higher in COPD patients than in passive smokers and controls. These results concluded reduction in FEV1&FEV1/FVC, Po2, serum A1AT, NO, ALB, Hb & PLT in COPD patients < passive smokers. Increase values of Pco2 plasma fibrinogen, serum CRP, sputum NO, (ALT &AST), (BUN & Creatinine) and (ESR, WBC &NE%) in COPD patients > passive smokers.