Hollow polymer capsules were prepared from linear as well as brushlike poly(2-oxazoline)s (POxs). Linear POxs containing alkene functionalities were obtained by cationic ring-opening polymerization (CROP), whereas the brush POxs bearing alkyne moieties were synthesized by a combination of CROP and reversible addition-fragmentation chain transfer (RAFT) polymerization. Multilayers consisting of POx/poly(methacrylic acid) (PMA) were sequentially deposited onto silica particle templates, and the films were stabilized either by thiol-ene (TE) chemistry or copper-catalyzed azide-alkyne cycloaddition (CuAAc). Stable, monodisperse capsules were formed after removal of the silica particles with hydrofluoric acid and were observed using fluorescence and atomic force microscopy (AFM). Both architectures exhibited low-fouling behavior, an essential criteria for therapeutic carriers to be utilized in bioapplications. In particular, the brush-like POx capsules show potential as a viable alternative material for the fabrication of low-fouling capsules.