The preeminent limitation of silicone membrane oxygenators is the poor gas permeability compared with microporous hollow fiber oxygenators (MHFO). However, the imponderability of plasma leakage, foam formation, and brittleness are all hazards that result in blood trauma formation, hereby limiting the application of MHFO during long-term oxygenation therapies. Here, we introduce a novel type of pure diffusive capillary-form silicone membrane called silicone hollow sphere. Silicone hollow sphere walls embed hollow microspheres into the core. The lodging of such microspheres promotes a higher gas exchange performance (as a result of the reduction of dense material) without altering the total thickness of capillary walls; thereby the demanded mechanical strength for handling is nevertheless conserved. Out of the same silicone material, seven SiHSp fibers with six different design specifications and a control were constructed to define experimentally the appropriate configuration for subsequent production. Each fiber was used in a miniaturized module oxygenator of a constant effective membrane surface area (Aeffmem = 0.02 m2) and length (L =183 mm) for a fair evaluation. Modules were investigated in vitro with porcine blood. O2 and CO2 transfer rates weighed 12.6 mlO2/min and 10.4 mlCO2/min, respectively, for one type of SiHSp, comparable with microporous polypropylene (OXYPHAN) exhibiting 14.1 mlO2/min and 13.2 mlCO2/min, respectively, at a maximum blood flow rate (Qmax = 200 ml/min). Silicone hollow sphere fibers show a promising competency to MHFs. They also show an evident dominancy over the conventional silicone fibers, evaluated by the control module, which emphasizes the advantage of this design.