Background The substitution hypothesis identifies absence constraints such as job and organizational demands as key precursors of presenteeism (attending work while ill). However, the relationship between absence constraints and presenteeism might be more complex than traditionally assumed (i.e., curvilinear). Moreover, it also remains unclear whether and how effective social support is in buffering these relationships. Purpose This study investigates whether the relationship between key absence constraints (i.e., attendance enforcement and work overload) and presenteeism follows a U-shaped curvilinear pattern and whether support mechanisms (i.e., colleague and manager support) moderate the absence constraints–presenteeism relationship. Methodology To answer these questions, we employed binary logistic regression analysis on survey data from a large and representative sample of nurses and midwives from Ireland (N = 1,037). Results The relationship between absence constraints and presenteeism is dependent on the type of absence constraint, with attendance enforcement demonstrating a curvilinear relationship and work overload demonstrating a linear relationship. Contrary to expectations, social support had limited impact on this relationship and acted as a “constraint in disguise” in the case of manager support and had no impact in the case of colleague support. Conclusion Our study challenges the basic tenets of the substitution hypothesis of presenteeism, particularly the idea that eliminating absence constraints always reduces the likelihood of presenteeism among nurses and midwives. Practice Implications Increasing support to reduce presenteeism is unlikely to be effective in controlling presenteeism among nurses and midwives. Hospitals would be better served by directly targeting the absence constraints of such presenteeism behavior.