Treatment with non-steroidal anti-inflammatory drugs (NSAID) after calving can have a positive effect on whole-lactation milk production in older dairy cows. Ongoing research aims to determine whether this response is due to increased mammary epithelial cell function and whether this is also tied to changes to inflammation in early lactation. For this study, cows in 3rd or greater lactation (n = 8/treatment) were enrolled at parturition to receive a daily drench of sodium salicylate (SS; 125g/d) or water (CON) for 3 d beginning approximately 24 h postpartum. Mammary biopsies were conducted on d 1, 4, and 45 after calving. Daily milk weights were recorded and milk composition was determined 2×/week. Blood samples were taken 2×/wk and analyzed for metabolites. Results up to 45 DIM show no difference between treatments for plasma glucose, insulin, β-hydroxybutyrate, or nonesterified fatty acid levels. Weekly means of milk production parameters revealed no detectable differences for fat content or yield, milk urea nitrogen, somatic cell score, energy-corrected milk yield, or fat-corrected milk yield. Treatment interacted with week for average protein yield (P = 0.02), with SS cows increasing more (1.07 to 1.49 ± 0.09 kg/d) over the 7 weeks of the study than CON (1.19 to 1.37 ± 0.09 kg/d). Lactose content tended to be greater for SS (4.89%) compared with CON (4.74 ± 0.05%; P = 0.06). Milk yield tended to increase more for SS (from 26.6 to 55.8 ± 2.6 kg/d) than CON (from 30.7 to 52.3 ± 2.3 kg/d) over time (interaction P = 0.10). Results agree with previous studies where milk production increased for salicylate-treated cows, although the small sample size in the present study limited power to observe production responses, and production data included only the first 45 d of lactation. Ongoing analysis of morphological and transcriptional changes in mammary tissue may reveal mechanisms that contribute to a sustained increase in milk production following early-lactation NSAID administration.