Diflucan (fluconazole) typically starts working within 24 to 48 hours for a yeast infection, with many people noticing a reduction in symptoms such as itching and irritation within that time frame. However, more noticeable improvements and a significant reduction in symptoms may take up to three days, and the infection may take up to a week to fully clear. If symptoms do not improve within three days or worsen, it is important to contact a healthcare provider. In some cases, a second dose may be prescribed if the first dose does not fully relieve symptoms.