Postpartum uterine disease is associated with reduced milk production and infertility in dairy cows. The reduction in milk production and infertility may be explained by acute disease (metritis) or chronic uterine inflammation (endometritis). Uterine disease may be a response to the uterine microbiome. The objective was to characterize the uterine microbiome at 7, 35, and 63 DIM using 16S rRNA gene sequencing. The hypothesis was that the uterine microbiome would change over time and that the composition would be associated with health and performance. The endometrium of 31 first parity dairy cows of Holstein and Jersey admixture was biopsied at 7, 35, and 63 DIM. DNA was extracted, and the V4 hypervariable region of the 16S rRNA gene was amplified and sequenced. Principal component analysis (PCA) identified a clustering of the samples such that the uterine microbiome at 35 and 63 DIM were similar, but different from the uterine microbiome at 7 DIM. In the same PCA, the 7 DIM samples separated into 2 distinct clusters that defined 2 groups of cows [A (n = 22) and B (n = 9)]. There was a greater number of reads per sample (P = 0.05) but lesser diversity (both Shannon and Chao1 P < 0.0001), and lesser abundance of the Ruminococcaceae family, Treponema spp. (both P < 0.0001), Streptococcus spp., and Prevotella spp. (both P = 0.02) in group A compared with group B. At 7 DIM, group A had a greater vaginal mucus score (VMS; P < 0.01) and 8% greater blood glucose concentrations (P = 0.04) compared with group B. Otherwise, cows from the 2 groups were similar for metabolic status, BW, BCS, body temperature and subsequent VMS. For their first 140 DIM, group A tended to have reduced SCS (3.93 vs. 4.69 units, P = 0.07) and greater ECM yield (25.81 vs. 23.40 kg/d; P = 0.1). The difference in ECM yield was greatest from wk 7 to 20 (Group x wk; P < 0.05). In summary, 2 groups of cows that differed in their uterine microbiome at 7 DIM also differed with respect to ECM yield but were largely similar with respect to other measures indicative of metabolic and uterine disease. These data raise the possibility that the early postpartum uterine microbiome impacts cow milk production in the absence of overt signs of disease.