Background Insect neuropeptides, mainly synthesized in the brain, play a central role in the control of many physiological processes. A neuropeptidome of the mosquito Nyssorhynchus albimanus was described based in a comparative analysis of the mosquito genome complemented with high-throughput sequencing of brain transcriptomes. In addition, neuropeptides differentially expressed during Plasmodium infection were identified.Results We identified 3,811 transcripts associated to translation, oxidation-reduction process, protein binding, ATP binding, integral components of membrane and ribosome, among others. We identified 29 neuropeptide transcripts that predicted at least 60 biopeptides, including pyrokinin, glycoprotein hormone alpha (GPA2), prothoracicotropic hormone, neuropeptide-like precursor 1 (NPLP1), allatostatin C, orcokinin, corazonin, adipokinetic hormone I, SIFamide, pyrokinin capa-like, pigment-dispersing factor, adipokinetic hormone/corazonin-related peptide (ACP), tachykinin-related peptide, trissin, neuropeptide F, short neuropeptide F (sNPF), diuretic hormone 31, bursicon, crustacean cardioactive peptide (CCAP), allatotropin, allatostatin 1, partner of bursicon (PBURS), ecdysis triggering hormone (ETH), diuretic hormone 44 (Dh44), insulin-like peptides 5, 1, 3, 7, 2 (ILPs) and eclosion hormone (EH) and seven neuropeptide receptors. Transcript mapping to the Ny. albimanus genome provided evidence for the re-annotation of the myosuppressin gene. A quantitative analysis documented increased expression of adipokinetic hormone/corazonin-related peptide, pyrokinin and corazonin in the mosquito brain after Plasmodium berghei infection.Conclusion This work represents an initial effort to characterize the neuropeptide repertoire of Ny. albimanus and provides new information for understanding neuroregulation of the mosquito response during Plasmodium infection .