Abstract The experiment was conducted to investigate the effects of antibiotics on blood profiles and serum inflammatory mediators of weaned pigs experimentally infected with F18 Escherichia coli (E. coli). Twenty-six pigs (6.88 ± 1.03 kg BW) were individually housed in disease containment rooms and randomly allotted to one of three treatments with 8–12 replicate pigs per treatment. The three dietary treatments were control diet and 2 additional diets supplemented with 0.5 or 50 mg/kg carbadox, respectively. The experiment lasted 18 d (7 d before and 11 d after first inoculation [d 0]). F18 E. coli inoculum was daily and orally as 1010 cfu/3 mL for 3 d. Blood samples were collected before E. coli inoculation and on d 2, 5, 8, and 11 post-inoculation (PI). Total and differential blood cell count were analyzed by CBC test. All data were analyzed by ANOVA using PROC MIXED of SAS. Supplementation of low-dose antibiotics had greatest (P < 0.05) neutrophils but lowest (P < 0.05) monocytes on d 2 PI, compared with control and high-dose antibiotics groups. Pigs in the low-dose antibiotics group still had higher (P < 0.05) white blood cell counts and lymphocytes than pigs in the other groups on d 11 PI. In consistent with CBC results, pigs supplemented with low-dose antibiotics had greatest (P < 0.05) serum C-reactive protein on d 2 and 5 PI and serum TNF-α on d 5 PI, compared with pigs in the control and high-dose antibiotics groups. No differences were observed in the red blood cell profiles between pigs in control and low-dose antibiotics groups, whereas supplementation of high-dose antibiotics had lowest (P < 0.05) packed cell volume but highest (P < 0.05) mean corpuscular hemoglobin concentration among three treatments. In conclusion, low-dose antibiotic supplementation may exacerbate systemic inflammation caused by F18 E. coli infection.