Three different SPE sorbents (weak cation exchange, mixed cation exchange, and hydrophobic-lipophilic balance polymers) were compared in terms of recovery, precision, and the effect of matrix components on analyte response for the determination of fluoroquinolones antibiotics. The influence of ethylenediaminetetraacetic acid disodium salt (Na2-EDTA) was as well tested. Two of the sorbents, hydrophilic-lipophilic balance (HLB) and weak cation exchange (WCX), turned out to be suitable for ultratrace analysis. HLB sorbent showed higher capacity for analyte trapping and better precision while weak cation exchange sorbent had a superior performance in terms of selectivity. In complex samples, the higher capacity of HLB was outweighed by the higher selectivity of WCX when considering the LODs of the methods.