High Field Asymmetric Waveform Ion Mobility (FAIMS) is an ion fractionation device attached front-end to an Orbitrap tribrid mass spectrometer that acts to separate and fractionate ions in the gas phase according to their physicochemical properties including charge, size, mass, and dipole moment. The use of FAIMS for cross-linking mass spectrometry (XL-MS), compared to traditional off-line fractionation techniques such as size-exclusion chromatography (SEC), has gained significant traction in recent years given its ability to enrich for low abundance cross-linked species. An advantage of FAIMS is the freedom it gives the user to modify the compensation voltage or combination of voltages applied to peptide ions allowing them to leave the device and enter the mass spectrometer. Therefore, the same sample can yield significantly different results based on the voltage scheme applied. Replicate LC-MS/MS analyses of Campylobacter jejuni whole cell protein digests and membrane proteins, fractionated with SEC and/or FAIMS and a combination of gradient lengths, were compared using a tribrid fragmentation scheme (CID-MS2-HCD-MS3-EThcD-MS2) and a combined compensation voltage approach with internal-stepping (CV= -50, -60, -75). For complex whole cell tryptic digests, the coupling of FAIMS to LC-MS/MS enabled a 3.2-fold increase in cross-linked spectral matches (CSMs) compared to without FAIMS, and a 2.3-fold increase in identifications compared to SEC fractionation. Single 180-minute gradient injections with FAIMS yielded greater than two-fold more CSMs and cross-linked peptides than any single SEC fraction or injection without differential ion mobility. The combination of FAIMS with SEC resulted in minimal differences in cross-link identification, highlighting a loss of orthogonality. Therefore, the usefulness of FAIMS lies in decreasing the sample amount, MS-time and sample preparation time needed for successful, rapid and in-depth analysis of complex cross-linked samples.