Bovine respiratory disease complex (BRDC) is a multi-factor disease, and disease incidence may be associated with an animal’s commensal microbiota (metagenome). Therefore, evaluation of the animal’s resident microbiota in the upper nasal cavity may help us to understand the effect of the metagenome on incidence of BRDC in cattle. Nasal swabs from approximately 600 calves were collected at various time points including preconditioning, weaning, and when the animal enters the feedlot and is diagnosed with BRDC. Samples from healthy cohorts were also collected for each time point evaluated in the feedlot to compare metagenome profiles of healthy and sick animals. Samples from animals diagnosed with BRDC in the feedlot were pooled in groups of 10 based on when the animal was diagnosed with BRDC (one week, 3 weeks, or 4 weeks after weaning). Samples from these same animals were also evaluated at the time points previous to entering the feedlot (preconditioning and weaning) to evaluate changes in the metagenome across time. Additionally, samples from the preconditioning and weaning time points were pooled in groups of 10 based on location origin of the animals before entering the feedlot, as calves came from 4 pasture locations before being weaned and comingled in the feedlot. To evaluate and compare the metagenome of each pooled sample, the variable region (approximately 1,500 bp) along the 16S ribosomal RNA gene was amplified by PCR to include v1-v8. These amplified products were then sequenced using next-generation sequencing (Pacific Biosciences RSII instrument) and sequence reads were analyzed by WebMGA and GreenGenes to identify subfamilies for the bacterial populations present. Overall, Mannheimia haemolytica (34–87%) was the predominant bacterial subfamily present in all pools evaluated at the feedlot, compared with preconditioning and weaning time points. Additionally, metagenome profiles differed across animal location origin before entering the feedlot. These results demonstrate a change in the metagenome of the nasal cavity across different time points of production and confirm the likely role of Mannheimia haemolytica in BRDC.