Colibacillosis is a complicated disease causing severe economic losses and challenging veterinarians and producers. Therefore, this study aimed to characterize avian pathogenic Escherichia coli (APEC) strains causing respiratory signs in chickens. Thirty broiler chicken flocks at age of 17-35 days showed respiratory signs and greenish diarrhea during 2013-2016 outbreaks that occurred in Sharkia, Ismailia, Dakahlia and Sinai Governorates. The postmortem findings revealed typical colisepticemia picture including air sacculitis, fibrinous pericarditis and perihepatitis. The percentage of APEC isolation was 100%. Mixed bacterial infections with Enterobacter aerogenes or Providencia rettgeri (3 flocks, each), Klebsiella pneumoniae (2 flocks), Serratia liquefaciens or Enterobacter agglomerans (1 flock, each) was evidenced. From 284 collected samples (air sacs, heart blood, lungs and liver), E. coli was predominantly isolated from air sacs (76.1 %) and lung (73.2 %) followed by heart blood (67.6%) and liver (54.9%). Based on serogrouping, the most common serogroups were O78 and O2 with percentages of 15%, each. Utilizing antimicrobial disc diffusion test, the isolates showed 32.7% resistance to doxycycline and 100% resistance to lincomycin, spiramycin, oxacillin and amoxicillin. Polymerase chain reaction (PCR) analysis for 55 MDR E. coli isolates from air sac and heart blood revealed 3 β-lactamase resistance genes; blaTEM (87.3 %), blaCTX-M (85.5 %) and blaOXA (5.5 %) and 6 virulence genes in two multiplex PCR; iucD (96.4%), Fim H (92.7%), iss (76.4%), ompT (58.2%), tsh (45.5%) and cvaC (9.1%). An association of virulence with multidrug resistance genes in E. coli was recorded, that hindered the control measures. Therefore, alternative strategies were necessary to minimize the antibiotic use and reduce the virulent strains' occurrence.