Background and Aim Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has profound effects on disease progression and patients’ quality of life. Emerging evidence suggests an association between alterations in the respiratory microbiome flora species and airway inflammation in patients with AECOPD. The present study aimed to describe the inflammatory cells and bacterial microbiome distributions in respiratory tract in Egyptian patients with AECOPD. Subjects and Methods The present cross-sectional study included 208 patients with AECOPD. Sputum and broncho-alveolar lavage samples from the studied patients were submitted to microbial cultures using appropriate media. Total and differential leukocytic counts and were done via automated cell counter. Results The present study included 208 AECOPD patients. They comprised 167 males (80.3%) and 41 females (19.7%) with an age of 57.9 ± 4.9 years. AECOPD was categorized as mild, moderate and severe in 30.8%, 43.3% and 26%, respectively. Sputum samples had significantly higher TLC, neutrophil percent and eosinophil percent when compared with BAL samples. In contrast, lymphocyte percent was significantly higher in BAL samples. Sputum specimens had significantly lower frequency of positive growths (70.2% versus 86.5%, p = 0.001). Among the identified organisms, sputum specimens had significantly lower frequency of Strept. pneumoniae (14.4% versus 30.3%, p = 0.001), Klebsiella pneumoniae (19.7% versus 31.7%, p = 0.024), Haemophilus influenzae (12.5% versus 26.9%, p = 0.011), Pseudomonas aeruginosa (2.9% versus 10%, p = 0.019) and Acinetobacter spp . (1.9% versus 7.2%, p = 0.012) growths when compared with BAL samples. Conclusion The present study could identify a distinctive pattern of inflammatory cell distribution in sputum and BAL samples of AECOPD patients. The most commonly isolated organisms were Klebsiella pneumoniae and Strept. pneumoniae .