High school students often find the concept of respiration difficult. Yeast, a readily available resource, offers promising material for studying the topic. This article describes a low-cost, microscale setup for investigating yeast fermentation. The observations in the practical activity are visually appealing to learners. The article also illustrates how this setup can be used to promote student engagement with scientific ideas by prompting students to (1) predict what they will observe in the activity and (2) link what they actually observe in it to the underlying scientific ideas, in the context of studying the effects of different sugar substrates on yeast fermentation. The simple setup can be easily modified for various scientific investigations related to yeast fermentation and, hence, represents a promising teaching tool for teaching this difficult-to-learn topic in high school biology classrooms.