The objective of the present study was to investigate the associations between major diseases (clinical mastitis, peracute mastitis, metabolic disorders, peripartum disorders) and four parameters related to productivity (305-day milk yield, number of days open, culling rate, death rate) on a large dairy farm in a temperate zone with approximately 2500 Holstein cows. Data were collected from 2014 to 2018 and involved 9663 calving records for 4256 cows. We found negative effects of clinical mastitis, peracute mastitis, metabolic disorders, and peripartum disorders on the productivity of cows. Clinical-mastitis-suffered cows with multiple diseases had more days open compared with those with clinical mastitis alone and the healthy group, and they had a higher death rate than the healthy group, whereas there was no difference in death rate between the clinical mastitis only and healthy groups. Cows suffering from peracute mastitis, metabolic disorders, and peripartum disorders with either single or multiple diseases exhibited reduced productivity compared with the healthy group. Our findings clearly show that major diseases of cows in a temperate zone have severely negative effects on their productivity.