The purpose of this study was to evaluate the effect of retained placenta (RP) and clinical mastitis (CM) on the reproductive efficiency of crossbred dairy cows during the postpartum period and to investigate the effect of them in some innate immune system indicators. For this, in the first experiment a total of 232 crossbred dairy cows were evaluated and divided into three groups as: healthy control, RP and CM. The incidence of RP and CM was evaluated after parturition until 30 days postpartum (DPP) and reproductive rates were measured. In experiment 2, 30 crossbred dairy cows were divided into three groups as in Experiment 1. Between 40 and 50 DPP, clinical, gynecological examination and endometrial cytobrush were performed to evaluate subclinical endometritis and gene expression of interleukin- 1β (IL-1β), interleukin-6 (IL-6), chemokine ligand -5 (CCL5), estrogen α (ESR1) and progesterone (PGR) receptors by qRT-PCR analysis. In Experiment 1, the conception rate at 1st AI was lower in RP and CM groups and pregnancy rate at 150 days decreased in cows with CM. Calving-to-1st AI interval and days open were shorter in healthy cows. In Experiment 2 the occurrence of subclinical endometritis was 26.7% and was higher in cows with RP and CM. The expression of IL-1β was increased in RP and CM groups, while IL-6 was less expressed in RP group. The chemokine CCL5, ESR1 and PGR were similar between groups. In conclusion, cows with RP and CM had their reproductive efficiency negatively affected and had they initial pro-inflammatory response improved by the increase of IL-β, while, IL-6 was lower in animals with RP probably because it was evaluated later in the postpartum.