Both milk fat-to-protein ratio (FPR) and blood metabolites such as β-hydroxy butyrate (BHB), glucose, and nonesterified fatty acids (NEFA) are frequently suggested as indicators of energy status in lactating cows. This study used a meta-analysis to identify if relationships exist between blood metabolites and FPR. The data set was collected from 20 experiments (67 treatments, 817 cows, mostly Holstein Friesian). Perennial ryegrass silage was the predominant forage source in all experiments (mean forage-to-concentrate DM ratio of 47:53). Samples for milk composition analysis were collected at least once every 2 weeks. Blood samples were normally taken between 1 and 2 h before feeding (sampling occasions = 894), while the frequency of blood sampling varied between studies (normally one sample every 14 to 28 d). Data were split into 3 periods (1–4, 5–8 and 9–12 weeks post calving). Relationships between individual blood parameters and FPR were examined using a Linear Mixed Model (REML estimation method). Study and cow within study were fitted as random effects in the model. The mean FPR (±SD) was 1.28 ± 0.215 for the entire 12 weeks period. For all blood parameters evaluated, relationships with FPR were most robust within each of the 3 time periods (R² ≥ 0.69) compared with the entire period (wk 1–12; R² ≥ 0.53). Beta-hydroxy butyrate was positively related to FPR whereas there was a negative relationship with glucose. Conversely, NEFA models were only significant (P = 0.05) for the wk 1–4 post calving, showing a positive relationship with FPR. Regression slopes of the linear equations were statistically different between the periods for both BHB and glucose (P < 0.05). Fat-to-protein ratio responses per unit of glucose (mmol/L) were more negative at wk 1–4 weeks (−0.045 FPR) compared with the observed responses after 5 wk post calving (−0.030 FPR). The results of this study indicate that empirical models could be established between BHB and glucose, and FPR, and it may be possible to integrate these to improve our understanding of energy balance during early lactation.