The present study investigated the decline in human fertility by analyzing the multielemental profile of seminal plasma and its relationship with seminal parameters and sperm biomarkers. Twenty-nine donor seminal plasma samples were examined using inductively coupled plasma–tandem mass spectrometry (ICP-MS/MS). Method optimization demonstrated that robust plasma conditions, including internal standardization and helium (He) collision gas, were essential to achieve reliable quantification. These conditions mitigated matrix effects and spectroscopic interferences, despite lower sensitivity. Elements such as copper (Cu), iron (Fe), manganese (Mn), strontium (Sr), titanium (Ti), vanadium (V), and chromium (Cr) were quantified, and several significant correlations were identified. Specifically, Cu was negatively correlated with seminal volume and positively correlated with sperm concentration and spontaneous acrosome reacted sperm, but negatively correlated with medium mitochondrial membrane potential (MMP); Mn showed negative associations with sperm vitality and medium MMP; Fe showed a negative correlation with motile sperm concentration (4 h); V was positively correlated with acrosome reacted sperm after acrosome reaction induction and with very low/medium MMP, whereas it was negatively associated with tyrosine phosphorylation; and Cr also showed a negative correlation with tyrosine phosphorylation. As, Mo, and Pb were detected in a few samples, limiting correlation analysis. From a functional perspective, elements such as As and Pb, as well as excess Cu or Fe, may contribute to oxidative stress by enhancing reactive oxygen species (ROS) generation and impairing antioxidant defenses. Conversely, essential metals, including Mn and Cu, at physiological concentrations act as cofactors of antioxidant enzymes and play a protective role against oxidative damage.