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<div><i>Pythium aphanidermatum</i> is the predominant species causing Pythium root rot on commercially grown poinsettias in NC. Mefenoxam (M) and fenamidone (F) are among the fungicides labeled for control of Pythium root rot on poinsettia. Widespread resistance to mefenoxam (MR) has been documented in <i>P. aphanidermatum</i>, but resistance to fenamidone and other QoIs has not been reported. <i>In-vitro</i> sensitivity (S) or insensitivity (R) to mefenoxam (17.6 μl a.i/ml) and fenamidone (488 μl a.i./ml) was tested on 96 isolates and the isolates were assigned to four fungicide resistance groups: MSFS, MRFS, MSFR, MRFR. 56% of isolates were insensitive to one (MRFS=35%; MSFR=15%) or both fungicides (MRFR = 6%). A single point mutation in the cytochrome-b gene (G143A) was identified in fenamidone-insensitive (FR) isolates. Mycelial growth rate, oospore production, and aggressiveness were evaluated to assess fitness of fungicide-resistant isolates. MRFR isolates had reduced growth rates at 30°C and were less aggressive on inoculated poinsettias than other isolate groups. MSFS isolates produced significantly more oospores <i>in-vitro</i> than isolates resistant to one or both fungicides. Fungicides failed to prevent disease on plants inoculated with resistant isolates, demonstrating the practical implications of resistance. This is the first report of QoI resistance in <i>P. aphanidermatum</i> from greenhouse floriculture crops and the first report of dual resistance to mefenoxam and QoIs.</div>