This study investigated the role of harmonic cancellation in the intelligibility of speech in “cocktail party” situations. While there is evidence that harmonic cancellation plays a role in the segregation of simple harmonic sounds based on fundamental frequency (F0), its utility for mixtures of speech containing non-stationary F0s and unvoiced segments is unclear. Here we focused on the energetic masking of speech targets caused by competing speech maskers. Speech reception thresholds were measured using seven maskers: speech-shaped noise, monotonized and intonated harmonic complexes, monotonized speech, noise-vocoded speech, reversed speech and natural speech. These maskers enabled an estimate of how the masking potential of speech is influenced by harmonic structure, amplitude modulation and variations in F0 over time. Measured speech reception thresholds were compared to the predictions of two computational models, with and without a harmonic cancellation component. Overall, the results suggest a minor role of harmonic cancellation in reducing energetic masking in speech mixtures.