The heat transfer, friction factor, and flow pattern of air/water mist flow in a rectangular minichannel heat sink were experimentally investigated. The channel size effect was studied using three horizontal minichannels exhibiting cross-sections measuring 0.5 mm × 3 mm, 1 mm × 3 mm, and 3 mm × 3 mm. The gas Reynolds number ranged from 1000 to 6000, and the wall temperature ranged from 40 to 60 °C. For the single-phase air flow, the flow transition was comparable with the conventional flow channel. For the mist flow, the flow patterns observed in the current minichannel were dry-wall mist flow and wavy annular flow. The mist cooling performance decreased with increase in wall temperature, mainly because of the extended dryout regions. The heat transfer from the mist flow was 1.5–4 times higher than the air flow, and higher enhancement ratios were observed in larger minichannels at lower gas Reynolds numbers. Because of droplet accumulation in the minichannel, the friction factor due to the mist flow was 2–3 times higher than the air flow. The friction factor decreased with increase in wall temperature because of the low volume of liquid in the minichannel.