Both Human Respiratory Syncytial virus (RSV) and Human Metapneumovirus (hMPV) cause immune-mediated under-five acute respiratory infections (ARI), but differences in their disease pathogenesis, if any, are not well-known. This study was undertaken to analyze the epidemio-clinico-immunological features of RSV and hMPV infections. Naso-pharyngeal aspirates from children (aged two months to five years) with ARI presenting to our tertiary care center between December 2013 to March 2016 were subjected to real-time polymerase chain reaction for detection of RSV and hMPV. Positive samples were analyzed for co-infections and levels of cytokines. Of 349 naso-pharyngeal aspirates, RSV was detected in 40.68% (142/349), hMPV in 6.59% (23/349) and both in 1.4% (5/349). Co-infections were common, rhinovirus being the commonest co-offender. The demographical and clinical parameters of RSV- and hMPV-infected children were comparable. MMP-9/TIMP-1 ratio was significantly higher in RSV-mediated ARI and IFN-γ in hMPV-mediated ARI. Both RSV and hMPV are common among north Indian children with ARI and coinfections are not uncommon. Their clinical features being non-discriminatory, molecular diagnosis should be utilized to ascertain their individual epidemiology. The differences in their immune-pathogenesis (MMP-9/TIMP-1 ratio in RSV and IFN-γ in hMPV) could serve as useful tools for developing newer drugs.