Intensiveness of hyperketonemia (HYK) detection protocols increases the desire to utilize less invasive strategies such as routine milk infrared analysis; however, milk infrared analysis of β-hydroxybutyrate (BHB) may mislead diagnosis of HYK. The objectives of this study were to determine temporal blood BHB patterns, mammary BHB uptake, and milk BHB in non-HYK or HYK cows. Mammary vein and tail vessel (representing arterial blood) blood samples from 23 Holstein cows were collected every 4h beginning after the pm milking and continued for 24h (7 blood samples) in wk1 and wk3 postpartum to determine arteriovenous differences (AVdiff). Cows were fed between 8 and 10 a.m. and milked twice daily (7AM, 7PM) and every milking was sampled during the period for mid-infrared spectrum analysis of milk BHB. Data were analyzed by PROC MIXED (SAS 9.4). Arterial BHB ≥ 1.2 was used for HYK diagnosis. Repeated measures models contained fixed effects of week, sampling time, and their interaction for temporal BHB analysis, or diagnosis, week, sampling time, and their interactions for AVdiff analysis, and both contained the random effect of sampling time relative to feeding time and cow. Arterial BHB and AVdiff before each milking were averaged or summed and compared with milk BHB using PROC CORR. Arterial BHB was lowest (P < 0.01) in the sample before and after the morning milking. AVdiff was greater in wk3 than wk1 (P < 0.01), and was 2 times greater (P = 0.02) in wk1, and 3 times greater in wk3 in HYK vs. non-HYK. Correlations between milk and blood BHB differed by HYK status. In HYK cows, milk BHB tended to be correlated with AVdiff mean (r = 0.32; P = 0.1) but not AVdiff sum, and correlated with the arterial mean (r = 0.49; P = 0.01) and tended to be correlated with the arterial sum (r = 0.35; P = 0.08). For non-HYK, milk BHB was not correlated (P > 0.3) to AVdiff and correlated with arterial sum (r = 0.32; P = 0.01) and mean (r = 0.44; P < 0.01). These data suggest AVdiff increases during the postpartum transition period and is greater for HYK. Milk infrared BHB is correlated with arterial BHB and AVdiff but the strength and pattern of correlation differs by HYK status.