The objectives of this study were to assess the effect of clinical and subclinical diseases on incidence of clinical Johne's disease (JD), and to determine the effect of clinical and subclinical diseases on incidence of fecal shedding after 305 days in lactation. 1297 cows from two Minnesota dairies were enrolled in the study after fecal samples were obtained during the close-up period. A second fecal sample was obtained from cows after at least 305 after calving (DIM) or at time of leaving the herd (sold/dead). Between 3-21 DIM, blood samples were obtained for Beta Hydroxy Butyrate (BHB) and serum total protein testing. Body condition score (BCS) was evaluated during the close-up period, within 21 DIM and at end of lactation. Clinical disease (milk fever, retained placenta, metritis, ketosis, displacement abomasum, lameness, mastitis, abortion over 180 days of pregnancy, and JD clinical signs) and reproductive performance data (days to first breeding, times bred, and days open) were recorded. Average DIM when JD clinical signs cows were culled (n=66) was 209. Factors associated with culling due to JD clinical signs included pneumonia (OR=2.3, 95%CI=1.23-4.37), positive fecal culture during the closeup period (OR=35, CI=18-69), serum total protein levels 0.7 (0.46-1.1), BCS during the closeup period 0.45 (0.26-0.78) and in the beginning and end of lactation 0.54 (0.33-0.87), mastitis 0.50 (0.24-1.10), and retained placenta 0.36 (0.11-1.16). Onset of fecal shedding at the end of the lactation was associated with pneumonia (OR=2.4 CI=1.3-4.3), milk fever (OR=5.0, CI=1.7-17.8), mastitis (OR=0.46, CI=0.22-0.93), and BCS in the end of the lactation (OR=0.40, CI= 0.25-0.66). The results provide insights into the role of other diseases on JD clinical signs and fecal shedding, which may enable us to better manage the disease early in the lactation.