The application of pig slurry as fertilizer in agriculture provides nutrients, but it can also contain veterinary medicines, including antibiotic residues (ABs), which can have an ecotoxicological impact on agroecosystems. Furthermore, uptake, translocation, and accumulation of ABs in crops can mobilize them throughout the food chain. This greenhouse study aims to assess AB uptake from soil fertilized with pig slurry and its phenotypical effects on Lactuca sativa L. The plants were cropped in loamy clay soil dosed at 140 kg total N/ha and containing antibiotics (lincomycin, sulfadiazine, oxytetracycline, and enrofloxacin) at different concentration levels (0, 0.05, 0.5, 5, 50, and 500 mg/kg fresh weight, fw). Whereas sulfadiazine (11.8 ng/g fw) was detected in lettuce leaves at the intermediate doses (0.5 mg/kg), lincomycin and its transformation products (hydroxy/sulfate) were only detected at the 50 mg/kg fw dose. In addition, increased AB doses in the pig slurry resulted in decreased lettuce fresh weight and lipid and carbohydrate content and became lethal to lettuce at the highest AB concentrations (500 mg/kg fw). Nevertheless, even at higher doses, the AB content in lettuce following pig-slurry fertilization did not pose any direct significant human health risk (total hazard quotient<0.01). However, the promotion of antimicrobial resistance in humans due to the intake of these vegetables cannot be ruled out.