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The objective of this article was to evaluate the effectiveness of a PDT protocol to treat fungal infections in critically ill patients. We developed a protocol using PDT as a therapy to reduce oral candidiasis in mechanically ventilated patients hospitalized in an intensive care unit (ICU). Only adults 18 + years of age, who presented clinical signs of oral candidiasis, and were mechanically ventilated were recruited to participate in the study. The protocol consisted of clinical and laboratorial procedures. Clinical procedures involved the application of the photosensitizer methylene blue 0.01% activated by a diode laser (660 nm, 90 J/cm2) for 1.5 min. Saliva samples were collected before and after the PDT session. Laboratorial procedures included counting the fungi colony-forming units (CFU) and identifying the fungi species. Ten patients met the inclusion criteria. The mean age was 62 years, and 57% were men. PDT was effective in reducing colony-forming units regardless of the Candida species. We observed an average reduction of 1.99 log10 (98.54%; SD = 1.45) in fungi CFU counting. We identified Candida tropicalis and Candida glabrata as the most common fungi species. Technological and non-invasive therapies such as PDT may benefit mechanically ventilated ICU patients with oral candidiasis. Considering the compromised health of these patients and the disadvantages conventional pharmacological treatment may have for them (e.g., systemic administration of drugs and fungal resistance), PDT rises as an alternative to treat oral candidiasis in critically ill patients. Using our protocol, we will conduct a large clinical trial as the next step.