Inclusion Criteria  Age: 18-65 Diagnosis of MDD and currently in a major depressive episode Capacity to give informed consent Score of at least 29 on the MADRS  Exclusion Criteria  Low affinity binders (LABs) for TSPO Genotype Hypersensitivity to celecoxib, sulfonamides, aspirin, other NSAIDs, or any component of the formulation; previous asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs Heptic impairment, heart failure, severe renal impairment, recent GI bleed, history of peptic ulcer disease, anemia or any other contraindication for celecoxib Poor CYP2C9 metabolizer Currently taking medications that interact with celecoxib (digoxin, antihypertensives, diuretics, anticoagulant or anti-platelet treatment, including aspirin) Use of herbs, drugs, or medications with anti-inflammatory or immunomodulatory properties (within 5 half-lives of starting celecoxib treatment) Unlikely to tolerate medication washout or the medication-free period following washout Participant considered at significant risk for suicide ECT within 1 month High potential for excessive drug/alcohol use during the treatment period (excluding nicotine or cannabis) Significant active physical illness or neurological deficit that may affect brain functioning or imaging Any PET contraindications, including if study imaging will result in the participant receiving greater exposure than the research limit, or if participant is currently pregnant, breastfeeding, or planning to conceive during the course of study participation