The article discusses the process of aeronautical structure assembly in the presence of a sealant between the parts to be joined. An attempt to estimate the influence of sealant on assembly quality in terms of variation analysis is presented. The sealant is considered a highly viscous liquid that is applied to the surfaces of the assembled parts before the start of the final assembly. The modeling approach is based on the simulation of two-way coupled fluid–structure interaction between fluid sealant and compliant structural parts. Reynolds lubrication approximation is used in the fluid dynamics problem and variational formulation of contact problem combined with static condensation is used in the structural one. The joining of two aircraft panels is used as a numerical test for demonstration of the developed approach. Various phenomena connected with the presence of sealant are demonstrated. In particular, the difference in the fastener loosening due to sealant flow between different types of fasteners is investigated. Results of variation simulation show that the presence of sealant should be considered among determining factors in the analysis of assembly quality.