The binary mixture of ampicillin sodium and sulbactam sodium is officially analyzed by HPLCrnbut they can not be simultaneously determined by the normal spectrophotometric techniquesrnsince their absorption spectra have a strong degree of overlapping.rnThis study applied four Chemometrics-a ssisted spectrophotometric techniques for thernsimultaneous determination of the two drugs without undergoing any physical separation:rnderivative spectrophotometry, derivative ratio technique, class ical least square techniques andrnprincipal component regression techniques.rnThe derivative spectrophotomet ric t echniques could not be successful since the overlappingrnabsorption spectra of the two drugs could not be resolved from each other by this t echnique.rnThe derivative ratio technique showed a better result since it has separated the two spectra torna better extent. The technique determi ned ampicil lin in t he mixture by using sulbactam sodiumrnas a divisor at 251 nm, 252nm & 253nm. The amount of sulbactam sodium was also determinedrnusing ampicillin sodium as a divisor at 205nm, 222nm & 245nm. The CLS and PCR methodsrnwere found to be capable of separating and hence determining the two drugs simultaneouslyrnbetter than the oth er t echniques as ca n be seen from the recovery res ults.rnThe recovery results by all techniques were acceptable and very close to the results obtained byrnthe officia l method and t herefore the techn ique can equivalently be used for the simultaneousrndetermination of the studied drugs.rnKey words: Chemometrics, Spectrophotometry, Ampicillin sodium, Sulbactam sodium.