Identification of mechanisms that regulate host responses during self-resolving inflammation are of wide interest. This is because therapeutics that activate the host response to clear infections will provide new leads to combat infections without weakening the immune response. Herein, we identified two new families of host-protective molecules in in mice during infections and in human tissues following both sterile and infectious challenge. Investigations of their physical properties demonstrated that they carried n-3 docosapentaenoic acid backbones, conjugated triene and diene-double bond systems, and an alcohol at carbon-13, thus they were termed 13-series resolvins (RvT). RvT demonstrated potent protective actions in Escherichia coli infections with ng/mouse activities. These molecules stimulated bacterial phagocytosis at pM-nM potencies, regulated inflammasome components with human phagocytes in vitro and mice in vivo, as well as increased mouse survival up to 60% during lethal infections. The production of these bioactive molecules during neutrophil-endothelial cell interactions was initiated by endothelial cyclooxygenase-2 (COX-2) that gave 13R-hydroxy-docosapentenoic acid. The biosynthesis of this intermediate was increased with atorvastatin via S-nitrosylation of COX-2. The host protective actions of atorvastatin and RvT’s proved additive in murine E.coli infections where they accelerated resolution of inflammation and increased >60% survival. RvTs and atorvastatin each engaged both overlapping and characteristic host protective pathways, including the upregulation of the anti-inflammatory eicosanoid prostaglandin I2 as well as the down regulation of the inflammation-initiating eicosanoids PGE2 and TXB2. Together these results identify novel host protective molecules poducted during both sterile inflammation and in bacterial infections, namely 13-series resolvins from n-3 docosapentaenoic acid. These molecules orchestrate key innate host protective responses in infections. In addition, these endogenous pathways can serve as statin-markers and may provide novel opportunities for limiting some of the unwanted responses to statins.