High-producing dairy herds where there is a predominant utilization of high-concentrate low-fiber diets can impair the buffering capacity of the rumen in dairy cows, and lead to a subacute ruminal acidosis (SARA). SARA is characterized by ruminal pH < 5.6 for extended hours. Decreased milk yield and milk efficiency, rumen epithelial damage, and laminitis are among several consequences of SARA. This study aimed to investigate the physiological adaptations during induced SARA in lactating Holstein cows. Eighteen cannulated cows were classified based on a retrospective analysis of pH after SARA induction, cows were grouped as non-SARA (n = 12) or SARA (n = 6) if ruminal pH was <5.6 for ~4 h regardless of treatment. SARA induction at d 5 (challenge) of trial was performed by giving a wheat/barley pellet at 10% of previous day DMI. Blood samples were collected on d 2, 5, 6, 7, and 8 of trial, and on d 5 at 0, 3, 6, and 12 h relative to the challenge. Data were analyzed using the PROC MIXED procedure of SAS, where group, hour, and day were fixed effects, while cow nested within group was the random effect. An interaction of Group × day (P = 0.01) was observed for haptoglobin with SARA group having greater concentration (0.23 vs 1.16 g/L) of this blood inflammatory biomarker on d 8 after challenge. Blood concentrations of creatinine and myeloperoxidase (P ≤ 0.04) were also greater in the cows subjected to challenge. Similarly, an interaction of Group × hour (P = 0.04) was observed for blood creatinine where cows challenged had greater concentration 6 h after induction. Concentrations of BHBA were greater (P < 0.01) during hours after SARA induction in SARA group. Overall, our results suggest that the metabolic and inflammatory profile in blood were more affected in cows induced to SARA regardless of treatment.