Simple SummaryA block randomized trial was conducted in California dairies to evaluate the effect of different treatments at dry-off on the subsequent lactation’s milk production and somatic cell count (SCC). Greater milk production was observed in cows treated with antibiotics and teat sealants at dry-off in comparison to controls, while there was no significant difference in the milk produced by cows that received either antibiotic or teat sealant in comparison to the untreated cows. Different dry cow treatments were associated with a reduction in ln SCC during the first 150 DIM, with the greatest reduction associated with both antibiotic and teat sealant in comparison to controls. Dairies with high SCC may benefit from treating cows at dry-off with AB, TS, or both.Mastitis is the greatest disease challenge for dairy producers, with substantial economic impacts due to lost milk production. Amongst the approaches implemented to control and prevent mastitis on dairies are vaccination, pre- and post-milking teat dips, and treatments at dry-off including intramammary antibiotics and teat sealants. The objectives of our study were to evaluate the effect of different treatments at dry-off on the subsequent lactation’s milk production and somatic cell count (SCC). A single-blinded controlled block randomized clinical trial was conducted between December 2016 and August 2018 on eight herds from four of the top ten milk-producing counties in California: Tulare, Kings, Stanislaus, and San Joaquin. The trial was repeated with cows enrolled during the winter and summer seasons to account for seasonal variability. Eligible cows were treated at dry-off with either intramammary antibiotics (AB), internal teat sealant (TS), AB + TS, or did not receive any treatment (control), and were followed through 150 days in milk (DIM) post-calving. The milk production and SCC data were extracted from monthly test day milk records (Dairy Comp 305, Valley Ag Software, Tulare, CA, USA). Two-piece spline linear mixed models were used to model the milk production (kg) and natural logarithm-transformed SCC. After accounting for parity, breed, season, and dry period duration, the milk model showed a significant increase in milk production (1.84 kg/day) in cows treated with AB + TS at dry-off in comparison to controls. There was no significant difference in the milk produced by cows that received either AB or TS (0.12 kg/day, and 0.67 kg/day, respectively) in comparison to the untreated cows. Different dry cow treatments were associated with a significant reduction in ln SCC during the first 150 DIM. The greatest reduction was associated with using AB + TS, followed by AB, and finally TS in comparison to controls. Dairies with high SCC may benefit from treating cows at dry-off with AB, TS, or both.