The remediation of oil sand process-affected water (OSPW) generated during the bitumen extraction in the oil sand region of Canada is an area of ongoing research interest. One of the primary remediation challenges is the removal of residual complex organic compounds present in the OSPW. In the present study, the molecular constitution of OSPW from aerated and nonaerated wetland treatments were characterized in constructed wetland treatment systems. Negative-ion and positive-ion atmospheric pressure photoionization (APPI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was used to provide extensive molecular-level analysis of the samples. Multiple aerated and nonaerated treatment wetland systems were characterized in terms of naphthenic acids (NAs), oxy-NAs, heteroatom NAs class, and double bond equivalent (DBE) versus carbon number to evaluate their molecular composition and variability. A broad range of heteroatom compound classes with variable relative abundances were identified. The DBE versus carbon number analysis revealed different levels of transformation of the compound classes, an indicator of NA fraction compound susceptibility to transformation. The selectivity and the extent of transformation of the compound classes were a function of the wetland design. The complementarity in the heteroatom classes detected in negative-ion and positive-ion APPI FT-ICR-MS highlight the need for multiple ionization methods for more complete coverage of the distribution of components in OSPW. The detailed molecular level information can be useful for prediction of the fate and associated toxicity of the species and also treatment efficiencies of the wetland systems.