The present study evaluated the effects of switching from fatty acids, n-6 polyunsaturated (PUFA) to n-3 (PUFA) supplements while maintaining constant lipogenic and glucogenic diets around calving period. A total of 30 Holstein cows, selected based on their body condition and parity, were divided into three treatment groups. The cows were blocked from 21 (± 2) days before calving to 42 days post-calving.The teatments included a group that received a basal diet (control group), a group that received basal diet with 1.38% dry matter (DM) of palm fat, a saturated fatty acid (SFA group), and a group received 5% (DM) of safflower seeds (source of n-6 PUFA) from day 21 before calving to the day 21 after calving and 3.85% (DM) of flaxseed (n-3, PUFA) from the day 21 to day 42 after calving (Omega group). The feed supplemented with saturated and PUFA could increase milk production in comparison to the control group. Beta-hydroxybutyrate (BHBA) concentration was significantly greater in the SFA and the Omega groups compared to the control group. Insulin levels before and after calving were greater in the Omega group than in the SFA group. Among the inflammatory and immune factors, the malondialdehyde (MDA) levels were significantly greater in the Omega group during the prepartum period and total antioxidant capacity in the SFA and Omega groups during the entire experiment. Consequently, supplementing n-6 PUFA during the close-up and n-3 PUFA during the early lactation period can increase milk production without affecting dry matter intake.