Introduction: Monocyte chemoattractant protein-1 (MCP-1) is elevated after acute myocardial infarction (AMI), and potentiates left ventricular (LV) remodeling in murine models of AMI. We examined the relationships between serum MCP-1, change in LV function and biomarkers related to remodeling in a cohort of AMI patients. Methods: Serum MCP-1 concentrations were measured in 100 patients (age 58.9 ± 12.0 years, 77% male) admitted with AMI and LV dysfunction, at baseline (mean 46 h), 12 and 24 weeks; cardiac magnetic resonance imaging and measurement of matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9 occurred at each time-point. Results: MCP-1 increased significantly from 697 [483, 997] pg/mL at baseline to 878 [678, 1130] pg/mL at 24 weeks (p > 0.001). MMP-3 concentration increased while MMP-9 decreased significantly over time; MMP-2 concentration did not change significantly. Baseline MCP-1 correlated with change in (Δ) LV end-systolic volume index (ΔLVESVI; r = -0.48, p = 0.01) and with ΔLV ejection fraction (ΔLVEF; r = 0.50, p = 0.02). However, ΔMCP-1 correlated positively with ΔLVESVI (r = 0.40, p = 0.006) and negatively with ΔLVEF (r = −0.36, p = 0.004). MCP-1 had no relationship with any MMP. Conclusions: MCP-1 may have a dichotomous role following AMI, aiding early infarct healing but potentiating later remodeling, which merits further study before any therapeutic trials of MCP-1 modulation in humans.