Objective: To examine the spectrum of pathogens and outcome of severe acute respiratory infections (SARIs) among admitted children with hematology/oncology disorders who presented with SARIs in low-middle income countries. Patients and methods: The prospective observation study recruited 52 children, clinically assessed, and their nasopharyngeal and oropharyngeal swabs were examined and analyzed by real-time multiplex PCR. Results: The children were 27 females and 25 males, mean age of 5.2 ± 2.9 years, 36 (69.2%) had pediatric malignancies, mostly (67%) hematologic malignancies, eight (15.4%) had chronic hemolytic anemia. Forty-eight (92.3%) presented with fever, 42 (80.7%) had a cough at the time of presentation. The median time from onset of symptoms till admission was 3.0 (1–6) days, and the median length of hospital stay was 9.0 days (4–16.5). Respiratory pathogens were detected in 39 (75%) samples, mostly Klebsiella pneumoniae (50%), Streptococcus pneumoniae (30.8%), Pdm H1N1 (33.3%), rhinoviruses (25.6%). Bacterial and viral pathogens codetected in 19 (48.7%) of cases. Five (9.6%) required pediatric ICU admission, four (7.7%) patients died during the study period; one died of respiratory failure, one of septic shock, and two died of their primary disease in the pediatric ICU. Conclusion: The present study added more insights about the viral and bacterial agents involved in SARI cases in Egypt in vulnerable pediatric groups.