Background: Whipple’s Disease (WD) is a chronic and recurrent multisystem disease caused by Tropheryma whipplei (TW). Typically, MTB infection compromises the immune system. However, clinical reports of MTB and TW co-infection are rare. Methods: This study retrospectively analyzed the admission symptoms and biochemical test results of 39 patients co-infected with MTB and TW between January 1, 2023, and August 31, 2024, at the Infectious Disease Hospital of Heilongjiang Province, China. This study further compared the admission indicators between individuals with co-infections involving more than two pathogens (multi-infected) and those infected with only MTB and TW (Co-Infected). Results: The hospitalized patients had a median age of 50 (39–58) years. Most of the patients were male (69.23%, 27/39). Most patients presented with cough (87.18%, 34/39), sputum production (76.92%, 30/39), shortness of breath (64.10%, 25/39), and reduced appetite or even anorexia (53.85%, 21/39). However, fever (41.03%, 14/39) and fatigue (41.03%, 16/39) were less common. Among the patients who underwent these four biochemical tests, the majority (86.36%, 19/22) had an A/G ratio below the normal range at the time of admission, primarily due to an increase in serum globulin levels. Multi-Infected group had higher levels of alanine aminotransferase than the Co-Infected group (17 vs. 10, p = 0.035), and aspartate aminotransferase is also higher in the multi-infected group compared to the Co-Infected group (20 vs. 14, p = 0.034). Conclusion: This is the first study to report the coinfection of Tropheryma whipplei (TW) and Mycobacterium tuberculosis (MTB) in Heilongjiang Province, China. However, this study did not find significant differences from descriptions in existing literature. Therefore, this study has provided a descriptive analysis to serve as a reference for further understanding TW infections.