A total of 240 newly weaned pigs (5.25 ± 0.15 kg BW) were used to determine the dietary omega-6-to-omega-3 (ω-6:ω-3) fatty acid ratio that optimized growth performance and immune responses when fed corn and soybean meal (SBM)-based diets with low protein quality. Pigs were randomly assigned to 1 of 5 dietary treatments (n = 6 pens per treatment; day 0 of study): [1] positive control (High; included animal proteins and 5% corn oil), [2] negative control (Low0; corn- and SBM-based and 5% corn oil), or 1 of 3 Low diets with increasing supplementation of fish oil to replace corn oil: [3] 1.25% (Low1.25), [4] 2.5% (Low2.5), [5] 5% (Low5) to achieve 5:1, 3:1, and 1:1 ω-6:ω-3 ratios, respectively. Pigs were fed dietary treatments in 2 phases for 7 and 14 d, respectively, followed by a common phase III diet for 21 d. On day 6 and 20, 12 pigs per treatment were immune sensitized with 0.5 mg ovalbumin (OVA) and 0.5 mg Quil A adjuvant in 1 mL saline. The dermal hypersensitivity response (DHR) was evaluated on day 40 in these same pigs, using intradermal injection of OVA; changes in skin-fold thickness were measured. On day 21, 4 pigs per pen were immune challenged with LPS (30 µg Escherichia coli LPS per kg BW) or saline (n = 12); rectal temperature was monitored over 3 h. During phase I only, ADG, ADFI, and G:F were greater for pigs fed the High diet vs. those fed the Low diet (P < 0.05), and increased with increasing fish oil supplementation up to 2.5% (Low2.5), but decreased for pigs fed the Low5 diet (quadratic; P < 0.05, P = 0.086, and P < 0.05 for ADG, ADFI, and G:F, respectively). On day 21, LPS increased rectal temperature (vs. saline at 1-, 2-, and 3-h post-challenge; P < 0.001); fish oil supplementation reduced rectal temperature 2-h post-challenge in the Low-fed pigs (linear; P < 0.05). On day 22, serum haptoglobin was greatest for pigs fed Low0 and decreased with increasing fish oil supplementation (linear; P < 0.05). Immunization with OVA induced a serum anti-OVA IgG response, which was reduced on day 34 among pigs fed Low diets with increasing fish oil supplementation (linear; P = 0.050). On day 40, and 6 h after intradermal injection of OVA, the DHR was least for pigs fed the Low2.5 diet (P < 0.05). Inclusion of 2.5% fish oil (3:1, ω-6:ω-3) optimized growth performance during the early nursery phase when pigs were most sensitive to diets with low protein quality; the ideal ω-6-to-ω-3 fatty acid ratio may differ when using immune responses as the major outcome.