One of the pressing current issues requiring investigation is the adverse effect of prolonged exposure of schoolchildren to substandard indoor climates and elevated CO₂ levels, which can impair their well-being, hinder cognitive performance, and disrupt the body's adaptive capabilities. This study aimed to assess the dynamics of mental performance of students depending on the said parameters, the indoor climate and CO₂ levels. The temperature, humidity, and CO₂ datapoints (n = 673) were recorded using an Engineering Technical Module in two rooms. Mental performance was assessed by the performance quotient and indicators of short-term memory and attention (n = 352); for this purpose, we used an NS-Psychotest hardware and software complex. In statistical processing, the threshold of significance was set at p < 0.05. We registered an increase of temperature up to 25.7 °C, a decrease of humidity to 31.3%, and a steady growth of the concentration of CO₂ from the normal 1000 ppm to substandard 2586 ppm. By the end of the day, the proportion of schoolchildren capable of high-level mental performance had dropped by 30%. We identified significant, moderately strong inverse correlations between performance level and CO₂ concentrations (r = −0.464, p < 0.001), as well as weak inverse correlations with temperature (r = −0.327, p < 0.001). A strong inverse relationship was found between fatigue and CO₂ levels (r = −0.599, p < 0.001); schoolchildren's functional state was poorest when the CO₂ concentration was highest. The study identified a correlation between the deterioration of air quality parameters and reduced mental performance among students, highlighting the necessity for monitoring and preventive interventions.