Purpose <p>To compare the magnitude of central, mid-peripheral and peripheral stromal corneal oedema induced during short-term fenestrated and non-fenestrated scleral lens wear.</p> Methods <p>Nine healthy participants wore a non-fenestrated and a fenestrated (0.3-mm diameter limbal fenestration) scleral lens (KATT™, Capricornia Contact Lenses), hexafocon B material (Dk 141 × 10⁻¹¹ cm³ O₂(cm)/[(s) (cm²) (mmHg)]) in one eye under open-eye conditions for 90 min on two separate days. Scleral lens thickness, fluid reservoir thickness and stromal corneal oedema were measured using high-resolution optical coherence tomography. Stromal oedema was quantified across the central (0–2.5 mm from the corneal apex), mid-peripheral (−3.0 to −1.0 mm from the scleral spur) and peripheral (−1.0 to 0 mm from the scleral spur) cornea with the lens in situ. The magnitude of oedema was corrected based on variations in fluid reservoir thickness between the lens conditions.</p> Results <p>There was a significant effect of lens type (<i>p</i> = 0.04) on stromal oedema, with less oedema observed with the fenestrated (0.36 ± 0.45%) compared to the non-fenestrated lenses (1.24 ± 0.27%), averaged across all corneal locations. A significant lens type by corneal location interaction was also observed (<i>p</i> = 0.05), with less oedema observed in the peripheral region for the fenestrated (−0.15 ± 0.98%) compared to the non-fenestrated lenses (1.81 ± 0.57%) (<i>p</i> = 0.048). A fenestration location by corneal location interaction was also observed (<i>p</i> = 0.02), indicating a greater reduction in oedema closer to the fenestration.</p> Conclusions <p>Central and mid-peripheral stromal oedema was similar during fenestrated and non-fenestrated lens wear; however, fenestrated lenses displayed significantly less oedema in the peripheral cornea. This is most likely due to increased oxygen delivery in proximity to the fenestration.</p>