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Vibrational spectroscopic techniques such as Raman spectroscopy and Fourier transform infrared spectroscopy (FTIR) have huge potential for the analysis of biological specimens. The techniques allow the user to gain label-free, non-destructive biochemical information about a given sample. Previous studies using vibrational spectroscopy with the specific application of diagnosing colorectal diseases such as cancer have mainly focused on in vivo or in vitro studies of tissue specimens using microscopy or probe based techniques. There have been few studies of vibrational spectroscopic techniques based on the analysis of blood serum for the advancement of colorectal cancer diagnostics. With growing interest in the field of liquid biopsies, this study presents the development of a high-throughput (HT) serum Raman spectroscopy platform and methodology and compares dry and liquid data acquisition of serum samples. This work considers factors contributing to translatability of the methodologies such as HT design, inter-user variability and sample handling effects on diagnostic capability. The HT Raman methods were tested on a pilot dataset of serum from 30 cancer patients and 30 matched control patients using statistical analysis via cross-validated PLS-DA with a maximum achieved a sensitivity of 83% and specificity of 83% for detecting colorectal cancer.