Nerve growth factor-β (NGF) is a seminal plasma protein that has been found to improve corpus luteum (CL) function in heifers. The objective of this study was to determine if systemic administration of NGF, purified from bovine seminal plasma, would enhance CL function and conceptus development in cows. Our hypothesis was that NGF administration at artificial insemination (AI) would increase progesterone (P4) production and expression of interferon-stimulated genes (ISGs) and pregnancy-specific protein B (PSPB), markers of conceptus development. NGF was purified from bull seminal plasma using a combination of anion and cation exchange chromatography and gradient elution. Beef cows were randomly assigned to CONT (n = 30) or NGF (n = 30) groups and synchronized using a 7-d Co-Synch + CIDR program. At time of AI (d 0), NGF cows received 296 µg purified NGF, reconstituted in 12 mL phosphate buffered saline intramuscularly. Blood samples were collected from each cow for quantification of peripheral P4 (d 0, 3, 7, 10, 14, 19) and PSPB (d 24) concentrations. Peripheral blood leukocytes were harvested at d 19 for measuring expression of ISGs (ISG15, MX1, MX2, RTP4) by qPCR. Pregnancy diagnosis was performed via ultrasonography exam on d 28 post AI. Statistical analysis was performed using ANOVA with repeated measures (SAS 9.4, Cary NC). NGF cows had increased plasma higher concentration of P4 than CONT cows from d 10–19 (P = 0.04). Pregnancy rates at 28 d were 75% in NGF cows versus 59% in CONT cows (P = 0.13). In pregnant cows, PSPB concentrations were higher in NGF than CONT cows (P < 0.05) at d 24. Additionally, expression of ISG15 and MX2 were greater in pregnant NGF cows than in pregnant CONT cows (P < 0.05) at d 19, but not significantly different for MX1 and RTP4 were present. Collectively, these results demonstrate that NGF administration at AI improved CL function and enhanced markers of conceptus development. Future studies are warranted to investigate whether NGF can be used to improve reproductive efficiency of cattle.