Single cell inductively coupled plasma mass spectrometry (scICPMS) enables quantitative analysis of individual cells, providing access to cellular heterogeneity that is obscured in bulk analyses. However, its analytical performance is strongly constrained by sample introduction efficiency, particularly for biological cells whose transport behaviour differs from those of standard solutions and nanoparticles. In this work, an infrared (IR)–heated pneumatic sample introduction system based on a modified cyclonic spray chamber, where the aerosol is pre-evaporated without solvent removal prior to entering the plasma, was employed for scICPMS analysis of a Se-enriched Saccharomyces cerevisiae (yeast) certified reference material (SELM-1) while monitoring the number of detected cell events. Multivariate optimization of IR-heating temperature, nebulizer gas flow rate, sample uptake rate, and sampling position was conducted. At 150 °C and 5 μL min?1 uptake rate, the IR-heated system achieved a cell transport efficiency of 47 ± 6%, representing a substantial improvement compared with a conventional cyclonic spray chamber (1.1 ± 0.4%) and exceeding that of a commercial single cell introduction system (30 ± 3%). Detection limits of 100–120 ag per cell were obtained for both ??Se and ?2Se. The Se mass per cell determined by scICPMS (65–68 fg cell?1) is consistent with independent estimates derived from certified total Se concentration and bulk digestion measurements, confirming analytical accuracy. Cell lysis occurred at IR-heating temperatures above 220 °C, emphasizing the necessity of optimization using cell-based matrices. Overall, this study demonstrates that controlled IR-heated sample introduction significantly enhances transport efficiency and enables reliable Se quantification in cells without requiring independent transport efficiency calibration.