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Background and aim: Microbes grow within a particular range of external pH, change of this pH may affect the respiratory pathogens. Our aim was to evaluate the effect of sodium bicarbonate (SB) 8.4% on the retrieved lower respiratory tract pathogens. Patients and methods: One hundred and twenty two patients with suspected lower respiratory tract infections were assigned randomly into 2 groups; 66 patients in group 1, who were subjected to broncho alveolar lavage (BAL) with 50 mL of 0.9% saline, then the retrieved BAL was divided into two equal volumes; one diluted with equal volume of saline and the other diluted with equal volume of SB (in vitro) and 56 patients in group 2, BAL with 10 mL of saline (a relatively small volume to avoid dilution and for detection of the organisms before the effect of SB) followed by BAL with 50 mL SB (in vivo). All samples were subjected to pH measurement and microbial detection. Results: There was a statistically significant decrease in median number of colony forming unit for bacteria and fungi in SB samples when compared to saline samples in group1 (in vitro) and in group 2 (in vivo). As regard to Mycobacterium TB, the number of positive cases for acid fast bacilli and culture for TB was less in SB samples when compared to saline samples in both groups. No significant complications related to the procedure were reported. Conclusions: SB 8.4% is a safe material and inhibitory for bacterial, fungal, and mycobacterial growth in the specific cultures and affects acid fast bacilli staining with Ziehl Neelsen.