Purpose In heart failure, dyssynchrony is associated with accelerated cardiac remodeling and a worse prognosis. Both restored with resynchronization. We have previously developed a mouse model of dyssynchrony and resynchronization and here assess changes in protein expression within that model. Experimental design Mice were subjected to ischemia/reperfusion followed by pacemaker implantation. Three groups were defined: (i) sinus rhythm four weeks - synchronous heart failure (SynHF), (ii) right ventricular pacing (RVP) four weeks - dyssynchronous heart failure (DysHF) and (iii) RVP two weeks followed by two weeks sinus rhythm - resynchronized heart failure (ResynHF). Heart tissue was evaluated for protein content with mass spectrometry. Results A total of 3324 proteins were detected. The abundance of 589 proteins differed between DysHF and SynHF and 253 between DysHF and ResynHF. The changed proteins in the comparisons to DysHF overlapped to a great extent. Among the dysregulated proteins in DysHF were several immunoglobulin chains and extracellular matrix proteins. Conclusion Adding dyssynchrony to ischemic heart failure resulted in protein dysregulation, which was partly reversed with resynchronization. The dysregulation was characterized by an increased immune activity and skewing of the extracellular matrix proteins, which may be part of the remodeling process in DysHF.