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Introduction: Methylene blue (MB) and hydroxocobalamin are routinely used for various shock states, but literature examining their efficacy when used together is limited. The objective of this study was to evaluate vasopressor requirement after sequential administration of methylene blue and hydroxocobalamin within 24 hours. Methods: A case series screening 72 patients who received MB or hydroxocobalamin was conducted if they were admitted to any AdventHealth hospitals between June 30, 2024, and July 31, 2025. Patients were included if they had received both MB and hydroxocobalamin within a 24 hour period, regardless of the order of administration. MB was allowed to have a continuous infusion if it did not overlap with hydroxocobalamin therapy. Vasopressor requirements and mean arterial pressure was collected for 30 minutes, 60 minutes, and 180 minutes. A secondary endpoint of 28 day mortality was also collected. Results: A total of 8 patients were included in the final analysis. For the primary endpoint of vasopressor requirements at 30 minutes after the infusions started, there was no difference in norepinephrine equivalence in the MB 0.86 mcg/kg/min vs hydroxocobalamin 0.81 mcg/kg/min (p=0.937), at 60 minutes post dose in the MB group 0.73 mcg/kg/min vs hydroxocobalamin 0.67 mcg/kg/min (p=0.917), or at 180 minutes post dose in the MB group 0.94 mcg/kg/min vs hydroxocobalamin 0.95 mcg/kg/min (p=0.818). The mean arterial pressure at 30 minutes after infusions started showed no difference in the MB group 67.2 mmHg vs hydroxocobalamin 72.8 mmHg (-25.59 to 14.26; p=0.54), at 60 minutes post dose in the MB group 67 mmHg vs hydroxocobalamin 82.2 mmHg (-36.58 to 6.25;p=0.146), or at 180 minutes post dose in the MB group 69 mmHg vs hydroxocobalamin 65mmHg (-7.01 to 15.01;p=0.433). For the secondary endpoint of overall mortality, 75% of patients died at 28 days. The average time from drug administration to the other was 3.25 hours. The time from shock to study drug administration was 12.6 hours. The most common disease state encountered was advanced liver disease or cardiovascular disease. Conclusions: In this case series of patients who received sequential methylene blue and hydroxocobalamin for vasoplegia, there was no difference in vasopressor requirements or mean arterial pressure at 30, 60 and 180 minutes.