Sub-millimetre micro-drilling of carbon fibre reinforced polymer (CFRP) is governed by size-effect physics that diverges qualitatively from conventional macro-scale drilling, yet the response of cryogenic cooling in this regime has not been systematically characterised. An exploratory cell-matched investigation was conducted at 0.8 mm drill diameter in bidirectional Toray T300/epoxy CFRP over a matrix of spindle speeds (3000–5000 rpm) and feed rates (10–30 mm/min) under dry (DEMD) and liquid-nitrogen-assisted (CEMD) environments. Cell-matched Wilcoxon signed-rank tests confirmed that CEMD increased thrust force and reduced both inner-wall surface roughness and exit delamination factor in every one of the nine matched parameter cells (
). Thrust force rose from a DEMD range of 3.17–5.94 N to a CEMD range of 4.23–8.99 N owing to cryogenic laminate stiffening; surface roughness fell by a mean of 15.9% (best cell
), and the minimum exit delamination factor was 1.16. The desirability-optimal condition (CEMD, 4000 rpm, 10 mm/min) achieved with against 1.31 dry. The cross-scale consistency of the surface-roughness improvement with macro-scale results supports a matrix-level rather than bulk-thermal interpretation of the cryogenic benefit, providing direct guidance for sub-millimetre CFRP machining in printed-circuit-board, micro-electromechanical-system and aerospace fastener-pilot applications.