The role of microbial coinfection in the pathogenesis of pneumonia in children is not well known. The aim of this work was to describe the prevalence of microorganism co-detection in nasopharyngeal samples (NPS) of pneumonia cases and control subjects and to study the potential association between nasopharyngeal microorganism co-detection and pneumonia. A case-control study was carried out from 2010 to 2014 in nine study sites located in low- or middle-income countries. The data from 888 children under 5 years of age with pneumonia (cases) and 870 children under 5 without pneumonia (controls) were analyzed. Nasopharyngeal samples were collected; reverse transcription polymerase chain reaction (RT-PCR) enabled the detection of five bacteria and 19 viruses. Multiple, mixed-effects logistic regression modeling was undertaken to evaluate the association between microorganism co-detection and pneumonia. A single Streptococcus pneumoniae colonization was observed in 15.2% of the controls and 10.1% of the cases (P = 0.001), whereas S. pneumoniae and a single virus co-detection was observed in 33.3% of the cases and in 14.6% of the controls (P < 0.001). Co-detections with rhinovirus, respiratory syncytial virus, parainfluenza virus, human metapneumovirus, and influenza virus were more frequent in the cases compared with the controls (P < 0.001) and were significantly associated with pneumonia in multiple regression analysis. The proportion of single virus detection without bacterial co-detection was not different between cases and controls (13.6% versus 11.3%, P = 0.13). This study suggests that coinfection of S. pneumoniae and certain viruses may play a role in the pathophysiology of pneumonia in children.