Respiratory microbial infections were a major health problems of Egyptian buffaloes and had economic looses in meat and milk production. That caused pneumonia leading to morbidity and mortality in intensive rearing system. The aim was to study some investigations on some bacterial and fungal causes respiratory infections in Egyptian buffalloes. That were by isolation and identification to detect molecularity and antibiogram sensitivities. The methodology were included samples collection, microbial isolation and identification, antibiogram technique, DNA extraction and PCR amplification protocol for microorganisms. in the present study was conducted to examine 100 nasal swabs of buffalos (1_5 years) reared on private farms at El Dakahlia Governorate showing symptoms of depression, reduced the feed intake, respiratory problems_ dyspnea with or without nasal discharge and pneumonia also 50 mouth swabs collected from mucous discharge of buffalos suffering from cough and sneezing. Pasteurella multocida (p. multocida ), Escherichia coli (E.coli) and Staphylococcus aureus( staph aureus) where isolated in percentage of (12%_7%_5%) from nasal swabs respectively and (8%_4%_4%) from mouth swabs respectively. The main isolated fungi were Aspergills fumigatus ( A. fumigatus) and Aspergillus flavous (A.flavous) that isolated percentage (11% and 5%) from nasal swabs respectively and (8% and 4%) from mouth swabs respectively . p. multocida were sensitive to enrofloxacin, spectinomycin, and trimethoprim-sulfamethoxazole, Multi-Drug Resistance (MDR) to amoxicillin, ciprofloxacin, gentamicin, streptomycin, and chloramphenicol. E. coli were sensitive to ciprofloxacin, enrofloxacin, spectinomycin, and chloramphenicol, had MDR to amoxicillin, gentamicin, streptomycin, and trimethoprim-sulfamethoxazole. Staph. aureus were sensitive to enrofloxacin, and spectinomycin, had MDR to amoxicillin, ciprofloxacin, gentamicin, streptomycin, trimethoprim- sulfamethoxazole, and chloramphenicol. A. fumigatus was sensitive to fluconazole, ketoconazole, nystatin, and amphotericin B, had MDR to clotrimazole. A. flavus were sensitive to fluconazole, ketoconazole, and nystatin, had MDR to clotrimazole, and amphotericin B., The PCR using the KMT1 gene confirmed P. multocida isolates, developed specific 457 bp molecular size bands. The 16s rRNA gene confirmed E. coli isolates, developed specific 662 bp molecular size bands. The Coagulase gene confirmed Staph. aureus isolates, developed specific 600-1000 bp molecular size bands. The Asphs gene confirmed A. fumigatus isolates, developed specific 180 bp molecular size bands. The aflR1 gene confirmed A. flavus isolates, developed specific 798 bp molecular size bands. It was concluded that the microbial respiratory infection affected farm health. It was recommended for taken animal health precaution for protection from respiratory microbial infection for safe farm health.