The fractional treatment handpiece of a fractional CO₂ laser system is typically equipped with a circular "distance gauge" that rests against the skin, ensuring the skin surface is positioned at the laser's focal point during treatment. The focal length of this handpiece is commonly 50 mm.

When the CO₂ laser is applied to a microscopic spot on the skin, water molecules absorb the laser energy and vaporize instantly. Immediate tissue whitening is visible, accompanied by smoke and a "burning" odor produced by protein combustion. Therefore, a smoke evacuation system is essential during treatment, and the operator should wear a mask.

In fractional CO₂ laser treatment, even at the focal point, the laser beam still forms a spot with a very small but finite diameter. It therefore has a certain irradiation area, which determines the "coverage rate" on the treated skin.

This microscopic spot diameter is approximately 0.1 mm. The focal spot diameter varies with laser wavelength: the shorter the wavelength, the smaller the focal spot diameter. Within such a tiny diameter, the laser energy density is extremely high. A portion of the water within the microscopic volume of irradiated skin is instantly vaporized, proteins undergo thermal denaturation, and some structural bonds are broken. In the central region where energy is even higher, tissue may detach and exfoliate in a feathery or flaky manner, achieving the desired destructive and ablative effect.