While previous research has shown that high syllable frequency can facilitate speech production at the level of phonological/phonetic encoding, little is known about its influence on prephonological processes, specifically lexical selection. The current study used a picture-word interference (PWI) task to (a) shed light on the stages of lexical access where syllable frequency is relevant, and (b) inform as to whether lexical selection is accomplished via competition among activated word options. Participants named pictures whose names had high-frequency (HF) and low-frequency (LF) first syllables while ignoring phonologically related (same first syllable) or unrelated distractor words that were presented simultaneously. Word frequency was also manipulated, as half of the targets were HF words, and half were LF words. Results revealed inhibitory syllable frequency effects in all conditions, such that targets with HF first syllables were named more slowly than targets with LF first syllables. However, inhibitory syllable frequency effects were exacerbated in conditions thought to reflect heightened lexical competition, specifically in the presence of phonologically related distractors and for targets with low word frequency. These findings reveal novel evidence for first-syllable frequency effects on lexical selection and offer further support for models proposing delays at lexical selection due to activation of nontarget competitors.