This paper details an experimental investigation on the influence of the size effect when slot-milling a CMSX-4 single-crystal nickel-based superalloy using 1 mm- and 4 mm-diameter TiAlN-coated tungsten carbide (WC) end-mills. With all tools having similar cutting-edge radii (r_e) of ~6 µm, the feed rate was varied between 25–250 mm/min while the cutting speed and axial depth of cut were kept constant at 126 m/min and 100 µm, respectively. Tests involving the Ø 4 mm end-mills exhibited a considerable elevation in specific cutting forces exceeding 500 GPa, as well as irregular chip morphology and a significant increase in burr size, when operating at the lowest feed rate of 25 mm/min. Correspondingly for the Ø 1 mm micro-end-mills, high levels of specific cutting forces up to ~1000 GPa together with severe material ploughing and grooving at the base of the machined slots were observed. This suggests the prevalence of the size effect in the chip formation mechanism as feed per tooth/uncut chip thickness decreases. The minimum uncut chip thickness (h_min) when micromilling was subsequently estimated to be less than 0.10 r_e, while this increased to between 0.10–0.42 r_e when machining with the larger Ø 4 mm tools.