Elevated lactate levels at 24 h are highly predictive of in-hospital mortality in adults with septic shock. Thiamin is closely involved in carbohydrate metabolism, and in thiamin-deficient states, increased lactic acid levels can be found, exacerbated by critical illness. This integrative literature review focused on the relationship between supplemental thiamin, lactate clearance, and impact on mortality in sepsis. A search in PubMed, Embase, and CINAHL was conducted for literature published between January 2016 and January 2021. We included observational studies and clinical trials with ≥10 participants. We excluded studies involving pediatric (<18 years old) populations, animal studies, case studies, dropout rate of >20%, nonhospitalized patients, or patients receiving comfort measures only. A total of 48 full-text articles were assessed for eligibility, with 15 evaluated for this integrative review. Included were five retrospective, two prospective observational, and eight randomized controlled trials. In almost all retrospective studies, thiamin administration was associated with decreased mortality, and in observational studies, with decreased lactate and improved clinical outcomes. In clinical trials, thiamin with or without vitamin C/hydrocortisone did not impact clinical outcomes or mortality. However, four trials testing intravenous thiamin 200-500 mg two to three times daily for up to 3 days reported improved lactate clearance. Thiamin supplementation may improve lactate clearance when administered in the first 24 h. Those deficient in thiamin may benefit more from supplementation. The combination of thiamin, vitamin C, and/or hydrocortisone may not be advantageous. Lactate reduction in response to thiamin needs further rigorous research.