Milk fat depression (MFD) is a multifactorial disorder that can be easily induced with high levels of polyunsaturated fatty acids (PUFA). However, little is known about how sugar or soluble fiber can improve the conditions of MFD and if performance can be enhanced. The aim of the current study was to investigate the effect of feeding diets with or without soybean oil and the replacement of a portion of the starch for sources of high Su and or high SF, on milk production. We hypothesized that the treatments with high Su or high SF would improve milk production performance when challenged with soy oil. Eight multiparous Holstein cows were randomly assigned to treatments, consisting of soybean oil (High PUFA; HF) or no soy oil (Low PUFA; LF), low (LSu; 4% DM) or high sugar (HSu; 9% DM), and low or high soluble fiber (SF; 6 or 12% DM). This resulted in 8 unique treatments, 2 PUFA levels: LF (2.5% EE) and HF (5% EE) and to a combination of Su and SF sequence [LSuLSF (4% Su, 6% SF); LSuHSF (4% Su, 12% SF); HSuLSF (9% Su, 6% SF); and HSuHSF (9% Su, 12% SF)] within PUFA level administered according to a split-plot, 4 × 4 Latin square design (21 d periods). Data were analyzed using the MIXED procedure of SAS with PUFA, period within PUFA, Su, and SF were fixed effects. High PUFA-fed animals had reduced milk fat yield, composition, and fat corrected milk (P < 0.01). In addition, MUN was reduced substantially with the high PUFA treatments (P < 0.01). There was no effect of sugar on DMI or milk fat production, but there was an interaction for DMI between PUFA level and SF (P = 0.01) where DMI decreased as SF level increased in the high PUFA-fed animals. Milk yield was increased with LSu-fed animals (P < 0.01), and there was also greater feed efficiency observed for LSu (P = 0.01). The results of the current study imply that replacing a portion of the starch with Su or SF does not ameliorate characteristic symptoms of MFD, but can alter DMI, milk production, and feed efficiency.